Yulmetyev, R. M., E-mail: email@example.com; Yulmetyeva, D. G.; Haenggi, P.
To discuss the salient role of statistical memory effects in human brain functioning, we have analyzed a set of stochastic memory quantifiers that reflects the dynamical characteristics of neuromagnetic responses of magnetoencephalographic signals to a flickering stimulus of different color combinations from a group of control subjects, and compared them with those for a patient with photosensitive epilepsy. We have discovered that the emergence of strong memory and the accompanying transition to a regular and robust regime of chaotic behavior of signals in separate areas for a patient most likely identifies the regions where the protective mechanism against the occurrencemore » of photosensitive epilepsy is located.« less
Yuen, Eunice S M; Sims, John R
Human photosensitive epilepsy models have been used as proof of principle (POP) trials for epilepsy. Photosensitive patients are exposed to intermittent photic stimulation and the reduction in sensitivity to the number of standard visual stimulation frequencies is used as an endpoint. The aim of this research was to quantify the predictive capabilities of photosensitive POP trials, through a survey of current literature. A literature search was undertaken to identify articles describing photosensitive POP trials. Minimally efficacious doses (MEDs) in epilepsy were compared to doses in the POP trials that produced 50-100% response (ED50-100). Ratios of these doses were calculated and summarised statistically. The search identified ten articles describing a total of 17 anti-epileptic drugs. Of these, data for both MED and ED50-100 were available for 13 anti-epileptic drugs. The average ratio of MED to ED50-100 was 0.95 (95% CI 0.60-1.30). The difference in MED to ED50-100 ratios between partial epilepsy (0.82) was not significantly different from that of generalised epilepsy (1.08) (p=0.51). Photosensitive POP trials are a useful tool to quantitatively predict efficacy in epilepsy, and can be useful as early and informative indicators in anti-epileptic drug discovery and development. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Myers, Candace T.; Leu, Costin; de Kovel, Carolien G. F.; Afrikanova, Tatiana; Cordero-Maldonado, Maria Lorena; Martins, Teresa G.; Jacmin, Maxime; Drury, Suzanne; Krishna Chinthapalli, V.; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann-Kathrin; Møller, Rikke S.; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna-Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Gaudio, Luigi Del; Boustred, Christopher; Schneider, Amy L.; Lench, Nicholas; Jocic-Jakubi, Bosanka; Covanis, Athanasios; Capovilla, Giuseppe; Veggiotti, Pierangelo; Piccioli, Marta; Parisi, Pasquale; Cantonetti, Laura; Sadleir, Lynette G.; Mullen, Saul A.; Berkovic, Samuel F.; Stephani, Ulrich; Helbig, Ingo; Crawford, Alexander D.; Esguerra, Camila V.; Kasteleijn-Nolst Trenité, Dorothee G. A.
Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2·17 × 10−5). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3·50 × 10−4). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research
Aydin-Ozemir, Zeynep; Terzibasioglu, Ege; Altindag, Ebru; Sencer, Serra; Baykan, Betul
Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients.
Wielaender, Franziska; Sarviaho, Riika; James, Fiona; Hytönen, Marjo K.; Cortez, Miguel A.; Kluger, Gerhard; Koskinen, Lotta L. E.; Arumilli, Meharji; Kornberg, Marion; Bathen-Noethen, Andrea; Tipold, Andrea; Rentmeister, Kai; Bhatti, Sofie F. M.; Hülsmeyer, Velia; Boettcher, Irene C.; Tästensen, Carina; Flegel, Thomas; Leeb, Tosso; Matiasek, Kaspar; Fischer, Andrea; Lohi, Hannes
The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization. PMID:28223533
Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian
Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.
Vaudano, Anna Elisabetta; Ruggieri, Andrea; Avanzini, Pietro; Gessaroli, Giuliana; Cantalupo, Gaetano; Coppola, Antonietta; Sisodiya, Sanjay M.
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
Spagnoli, Carlotta; Kugathasan, Umaiyal; Brittain, Helen; Boyd, Stewart G
Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
da Silva, E A; Müller, R A; Chugani, D C; Shah, J; Shah, A; Watson, C; Chugani, H T
Intermittent photic stimulation (IPS) is an activation procedure used during electroencephalogram (EEG) recording to elicit paroxysmal discharges in individuals with photosensitivity. Specific responses on EEG recording may be provoked by IPS at different frequencies of flickering in normal individuals and in patients with photosensitive epilepsy. Changes in regional cerebral blood flow (rCBF) were studied during IPS in two groups of subjects by using [15O]-water positron emission tomography (PET): a control group consisting of eight healthy adults with photic driving response during IPS on EEG recording (mean age, 25 +/- 10.5 years) without history of neurologic or psychiatric abnormalities and a patient group consisting of four adults (mean age, 33 +/- 7.5 years) with history of photosensitive epilepsy. [15O]-water PET scanning with concomitant EEG monitoring was performed during baseline and IPS at 4-, 14-, and 30-Hz frequencies. The control group showed photic driving response at 14-Hz IPS frequency. The patient group showed photoparoxysmal response at 14 and 30 Hz, but not at 4 Hz. Changes in rCBF were determined by means of statistical parametric mapping. Increases in rCBF in occipital cortex (Brodmann's areas 17, 18, and 19) were observed in both groups. In addition, during photic driving responses, the control group showed rCBF increases in the insula and in the thalamus, on the right side. The patient group showed a significant rCBF increase in the hypothalamic region inferior to the left caudate nucleus during photoparoxysmal response. This activation was not found in the control group. Increased rCBF also was observed in the patient group in the head of the left caudate nucleus, in the left hippocampus, and in left insula during IPS without photoparoxysmal response. No activations in these regions were observed during photoparoxysmal response. These data may indicate involvement of the hypothalamus in photosensitive epilepsy and may suggest a modulatory
Lipton, R. B.; LeValley, A. J.; Hall, C. B.; Shinnar, S.
Clinicians often encounter patients whose neurologic attacks appear to cluster. In a daily diary study, the authors explored whether clustering is a true phenomenon in epilepsy and can be identified in the clinical setting. Nearly half the subjects experienced at least one episode of three or more seizures in 24 hours; 20% also met a statistical clustering criterion. Utilizing the clinical definition of clustering should identify all seizure clusterers, and false positives can be determined with diary data. PMID:16247068
Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl
Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.
Sha, Zhiqiang; Sha, Longze; Li, Wenting; Dou, Wanchen; Shen, Yan; Wu, Liwen; Xu, Qi
Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
... Staying Safe Videos for Educators Search English Español Epilepsy KidsHealth / For Teens / Epilepsy What's in this article? ... embarrass himself or scare his friends. What Is Epilepsy? Epilepsy is a condition of the nervous system ...
... Staying Safe Videos for Educators Search English Español Epilepsy KidsHealth / For Kids / Epilepsy What's in this article? ... Epilepsy Different? Print en español Epilepsia What Is Epilepsy? Epilepsy comes from a Greek word meaning "to ...
Chipaux, Mathilde; Szurhaj, William; Vercueil, Laurent; Milh, Mathieu; Villeneuve, Nathalie; Cances, Claude; Auvin, Stéphane; Chassagnon, Serge; Napuri, Sylvia; Allaire, Catherine; Derambure, Philippe; Marchal, Cécile; Caubel, Isabelle; Ricard-Mousnier, Brigitte; N'Guyen The Tich, Sylvie; Pinard, Jean-Marc; Bahi-Buisson, Nadia; de Baracé, Claire; Kahane, Philippe; Gautier, Agnès; Hamelin, Sophie; Coste-Zeitoun, Delphine; Rosenberg, Sarah-Dominique; Clerson, Pierre; Nabbout, Rima; Kuchenbuch, Mathieu; Picot, Marie-Christine; Kaminska, Anna
To obtain perspective on epilepsy in patients referred to tertiary centers in France, and describe etiology, epilepsy syndromes, and identify factors of drug resistance and comorbidities. We performed a cross-sectional analysis of the characteristics of 5,794 pediatric and adult patients with epilepsy included in a collaborative database in France between 2007 and 2013. Comparisons between groups used Student's t-test or Fisher's exact test for binary or categorical variables. Factors associated with drug resistance and intellectual disability were evaluated in multi-adjusted logistic regression models. Mean age at inclusion was 17.9 years; children accounted for 67%. Epilepsy was unclassified in 20% of patients, and etiology was unknown in 65%, including those with idiopathic epilepsies. Etiologies differed significantly in adult- when compared to pediatric-onset epilepsy; however, among focal structural epilepsies, mesial temporal lobe epilepsy with hippocampal sclerosis began as often in the pediatric as in adult age range. Drug resistance concerned 53% of 4,210 patients evaluable for seizure control and was highest in progressive myoclonic epilepsy (89%), metabolic diseases (84%), focal cortical dysplasia (70%), other cortical malformations (69%), and mesial temporal lobe epilepsy with hippocampal sclerosis (67%). Fifty-nine percent of patients with focal structural epilepsy and 69% with epileptic encephalopathies were drug resistant; however, 40-50% of patients with West syndrome and epileptic encephalopathy with continuous spike-and-waves during sleep were seizure-free. Ages at onset in infancy and in young adults shared the highest risk of drug resistance. Epilepsy onset in infancy comprised the highest risk of intellectual disability, whereas specific cognitive impairment affected 36% of children with idiopathic focal epilepsy. Our study provides a snapshot on epilepsy in patients referred to tertiary centers and discloses needs for diagnosis and treatment
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters ... may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, ...
Wang, Yimin; Du, Xiaonan; Bin, Rao; Yu, Shanshan; Xia, Zhezhi; Zheng, Guo; Zhong, Jianmin; Zhang, Yunjian; Jiang, Yong-hui; Wang, Yi
Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children. PMID:28074849
Devinsky, Orrin; Vezzani, Annamaria; O'Brien, Terence J; Jette, Nathalie; Scheffer, Ingrid E; de Curtis, Marco; Perucca, Piero
Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies. In addition, one-third of patients will continue to have uncontrolled seizures. Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications. In addition, seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies.
Dixit, Abhijit; Suri, Mohnish
Identifying the underlying cause of epilepsy often helps in choosing the appropriate management, suggests the long-term prognosis and clarifies the risk of the same condition in relatives. Epilepsy has many causes and a small but significant proportion of affected people have an identifiable genetic cause. Here, we discuss the role of genetic testing in adults with epilepsy, focusing on dysmorphic features noticeable on physical examination that might provide a strong clue to a specific genetic syndrome. We give illustrative examples of recognisable facial 'gestalt'. An astute clinician can recognise such clues and significantly shorten the process of making the underlying diagnosis in their patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Fisher, R.S.; Frost, J.J.
As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18(F)FDG inmore » some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18(F)FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.95 references.« less
Saipetch, Chutima; Sachs, Ezekiel
Abstract Purpose of review: Technological advance has revolutionized epilepsy management recently. Herein, we review some recent developments. Recent findings: Responsive neurostimulation (Food and Drug Administration [FDA]-approved 2013) works by continuous analysis of brain rhythms and direct brain stimulation on detecting patterns thought to be epileptogenic, thereby aborting seizures. Cardio-responsive vagus nerve stimulation (FDA-approved 2015) is an improvement over traditional vagus nerve stimulation systems, taking advantage of the fact that 80% of seizures are associated with tachycardia. Automated tachycardia detection leads to vagus nerve stimulation to abort seizures. In MRI-guided stereotactic laser ablation (developed 2012), a directed laser emitting fiberoptic catheter is used to ablate epileptogenic lesions. The procedure can be completed in 3 to 4 hours, potentially under local anesthesia and with next-day discharge. Perampanel (FDA-approved 2012) is a promising new class of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-antagonist antiseizure therapy. Meanwhile, a millennia-old remedy for epilepsy, cannabis, is staging a comeback with recent legal and social permissiveness accelerating research into this use. Summary: The coming years will demonstrate how these recent advances in device and drug management will improve the care of epilepsy. PMID:29443283
Verrotti, A; Tocco, A M; Salladini, C; Latini, G; Chiarelli, F
Photosensitivity is a condition detected on the electroencephalography (EEG) as a paroxysmal reaction to Intermittent Photic Stimulation (IPS). This EEG response, elicited by IPS or by other visual stimuli of daily life, is called Photo Paroxysmal Response (PPR). PPRs are well documented in epileptic and non-epileptic subjects. Photosensitivity rarely in normal individuals evolves into epilepsy. Photosensitive epilepsy is a rare refex epilepsy characterized by seizures in photosensitive individuals. The development of modern technology has increased the exposition to potential seizure precipitants in people of all ages, but especially in children and adolescents. Actually, videogames, computers and televisions are the most common triggers in daily life of susceptible persons. The mechanisms of generation of PPR are poorly understood, but genetic factors play an important rule. The control of visually induced seizures has, generally a good prognosis. In patients known to be visually sensitive, avoidance of obvious source and stimulus modifications are very important and useful to seizure prevention, but in the large majority of patients with epilepsy and photosensitivity antiepileptic drugs are needed.
Mishra, Vikas; Gautier, Nicole M; Glasscock, Edward
In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can potentially increase risk of sudden unexpected death in epilepsy (SUDEP). Electroencephalography (EEG) and electrocardiography (ECG) are widely used clinical diagnostic tools to monitor for abnormal brain and cardiac rhythms in patients. Here, a technique to simultaneously record video, EEG, and ECG in mice to measure behavior, brain, and cardiac activities, respectively, is described. The technique described herein utilizes a tethered (i.e., wired) recording configuration in which the implanted electrode on the head of the mouse is hard-wired to the recording equipment. Compared to wireless telemetry recording systems, the tethered arrangement possesses several technical advantages such as a greater possible number of channels for recording EEG or other biopotentials; lower electrode costs; and greater frequency bandwidth (i.e., sampling rate) of recordings. The basics of this technique can also be easily modified to accommodate recording other biosignals, such as electromyography (EMG) or plethysmography for assessment of muscle and respiratory activity, respectively. In addition to describing how to perform the EEG-ECG recordings, we also detail methods to quantify the resulting data for seizures, EEG spectral power, cardiac function, and heart rate variability, which we demonstrate in an example experiment using a mouse with epilepsy due to Kcna1 gene deletion. Video-EEG-ECG monitoring in mouse models of epilepsy or other neurological disease provides a powerful tool to identify dysfunction at the level of the brain, heart, or brain-heart interactions.
Hardie, Roger C
The Drosophila "transient receptor potential" channel is the prototypical TRP channel, belonging to and defining the TRPC subfamily. Together with a second TRPC channel, trp-like (TRPL), TRP mediates the transducer current in the fly's photoreceptors. TRP and TRPL are also implicated in olfaction and Malpighian tubule function. In photoreceptors, TRP and TRPL are localised in the ~30,000 packed microvilli that form the photosensitive "rhabdomere"-a light-guiding rod, housing rhodopsin and the rest of the phototransduction machinery. TRP (but not TRPL) is assembled into multimolecular signalling complexes by a PDZ-domain scaffolding protein (INAD). TRPL (but not TRP) undergoes light-regulated translocation between cell body and rhabdomere. TRP and TRPL are also found in photoreceptor synapses where they may play a role in synaptic transmission. Like other TRPC channels, TRP and TRPL are activated by a G protein-coupled phospholipase C (PLCβ4) cascade. Although still debated, recent evidence indicates the channels can be activated by a combination of PIP2 depletion and protons released by the PLC reaction. PIP2 depletion may act mechanically as membrane area is reduced by cleavage of PIP2's bulky inositol headgroup. TRP, which dominates the light-sensitive current, is Ca(2+) selective (P Ca:P Cs >50:1), whilst TRPL has a modest Ca(2+) permeability (P Ca:P Cs ~5:1). Ca(2+) influx via the channels has profound positive and negative feedback roles, required for the rapid response kinetics, with Ca(2+) rapidly facilitating TRP (but not TRPL) and also inhibiting both channels. In trp mutants, stimulation by light results in rapid depletion of microvillar PIP2 due to lack of Ca(2+) influx required to inhibit PLC. This accounts for the "transient receptor potential" phenotype that gives the family its name and, over a period of days, leads to light-dependent retinal degeneration. Gain-of-function trp mutants with uncontrolled Ca(2+) influx also undergo retinal degeneration
Wagner, Janelle L; Wilson, Dulaney A; Smith, Gigi; Malek, Angela; Selassie, Anbesaw W
To determine the distribution and risk characteristics of comorbid neurodevelopmental and mental health comorbidities among children and adolescents (6-18y) with epilepsy or migraine (i.e. a neurological condition with shared features and potential etiology) compared with lower extremity fracture (LEF). This case-control study involved a subset analysis of surveillance data in South Carolina, USA. Hospital admission, outpatient, and emergency department visits for individuals with an International Classification of Disease, 9th revision Clinical Modification diagnosis of epilepsy (n=6730; 54.5% females, 45.5% males; mean age [SD] 14y 2mo [4y 5mo]); migraine (n=10 495; 74.5% females, 25.5% males; 15y 6mo [2y 6mo]), or LEF (n=15 305; 40.3% females, 59.7% males; 13y 11mo [2y 11mo]) from January 1 2000 to December 31 2011 were identified. The association of epilepsy, migraine, or LEF with any mental health comorbidity was evaluated with univariate and multivariate polytomous logistic regression. Comorbidities were highly prevalent in children and adolescents, with epilepsy with a rate of 29.7% (95% confidence interval [CI]: 28.6-30.8) for mental health comorbidities and 30.8% (95% CI: 29.7-31.9) for neurodevelopmental comorbidities. The odds of mental health comorbidity was 2.20 (95% CI: 2.02-2.39) for children and adolescents with epilepsy and 1.60 (95% CI: 1.48-1.73) for migraine, in reference to children and adolescents with LEF after adjusting for potential confounders. Prevalence and risk for specific comorbidities are presented. Neuropathophysiological and psychosocial factors specific to epilepsy may provide more risk for adolescents with epilepsy compared to migraine. © 2014 Mac Keith Press.
Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico
Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized. PMID:24384641
In vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Chlorophyll-a and Bacteriochlorophyll-a
Srivatsan, Avinash; Wang, Yanfang; Joshi, Penny; Sajjad, Munawwar; Chen, Yihui; Liu, Chao; Thankppan, Krishnakumar; Missert, Joseph R.; Tracy, Erin; Morgan, Janet; Rigual, Nestor; Baumann, Heinz; Pandey, Ravindra K.
Among the photosensitizers investigated, both ring-D and ring-B reduced chlorins containing the m-iodobenzyloxyethyl group at position-3 and a carboxylic acid functionality at position-172 showed highest uptake by tumor cells and light-dependent photo reaction that correlated with maximal tumor-imaging [positron emission tomography (PET) and fluorescence] and long-term photodynamic therapy (PDT) efficacy in BALB/c mice bearing Colon26 tumors. However, among the ring-D reduced compounds, the isomer containing 1′-m-iobenzyloxyethyl group at position-3 was more effective than the corresponding 8-(1′-m-iodobenzyloxyethyl) derivative. All photosensitizers showed maximum uptake by tumor tissue 24h after injection and the tumors exposed with light at low fluence and fluence rates (128 J/cm2, 14 mW/cm2) produced significantly enhanced tumor eradication than those exposed at higher fluence and fluence rate (135 J/cm,2 75mW/cm2). Interestingly, dose-dependent cellular uptake of the compounds and light-dependent STAT3 dimerization have emerged as sensitive rapid indicators for PDT efficacy in vitro and in vivo and could be used as in vitro/in vivo biomarkers for evaluating and optimizing the in vivo treatment parameters of the existing and new PDT candidates. PMID:21842893
Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible.
Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible. PMID:29568622
Rand, Barry P; Forrest, Stephen R
The present invention generally relates to organic photosensitive optoelectronic devices. More specifically, it is directed to organic photosensitive optoelectronic devices having a photoactive organic region containing encapsulated nanoparticles that exhibit plasmon resonances. An enhancement of the incident optical field is achieved via surface plasmon polariton resonances. This enhancement increases the absorption of incident light, leading to a more efficient device.
Forrest, Stephen R.; Bailey-Salzman, Rhonda F.
The present disclosure relates to organic photosensitive optoelectronic devices grown in an inverted manner. An inverted organic photosensitive optoelectronic device of the present disclosure comprises a reflective electrode, an organic donor-acceptor heterojunction over the reflective electrode, and a transparent electrode on top of the donor-acceptor heterojunction.
Carter, Julie A; Molyneux, Catherine S; Mbuba, Caroline K; Jenkins, Jo; Newton, Charles R J C; Hartley, Sally D
Many people with epilepsy (PWE) in resource-poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision. Copyright © 2012 Elsevier Inc. All rights reserved.
Brunquell, Phillip J.
This paper discusses what epilepsy is and what it is not, defines types of epileptic seizures, identifies epilepsy syndromes, discusses antiepileptic drugs, describes seizure surgery, and examines issues of quality of life. (JDD)
Bureau, Michelle; Hirsch, Edouard; Vigevano, Federico
Since the first case of videogame (VG) epilepsy was reported in 1981, many cases of seizures triggered by VGs were reported, not only in photosensitive, but also in non-photosensitive children and adolescents with epilepsy. We provide an overview of the literature with overall conclusions and recommendations regarding VG playing. Specific preventive measures concerning the physical characteristics of images included in commercially available VGs (flash rate, choice of colors, patterns, and contrast) can lead in the future to a clear decrease of this problem. In addition to the positive effect of such measures, the collaborative studies performed in France and in the rest of Europe have stressed the importance of a safe distance to the screen of > or = 2 m, and the less provocative role of 100-Hz screens.
Vermeulen, Joost; Kalitzin, Stiliyan; Parra, Jaime; Dekker, Erwin; Vossepoel, Albert; da Silva, Fernando Lopes
Photosensitive epilepsy (PSE) is the most common form of reflex epilepsy. Usually, to find out whether a patient is sensitive, he/she is stimulated visually with, e.g. a stroboscopic light stimulus at variable frequency and intensity until a photo paroxysmal response (PPR) occurs. The research described in this work aims to find whether photosensitivity can be detected without provoking a PPR. Twenty-two subjects, 15 with known photosensitivity, were stimulated with visual stimuli that did not provoke a PPR. Using an "evoked response representation", 18 features were analytically derived from EEG signals. Single- and multi-feature classification paradigms were applied to extract those features that separate best subjects with PSE from controls. Two variables in the "evoked response representation", a frequency term and a goodness of fit term to a particular template, appeared to be best suited to make a prediction about the photosensitivity of a subject. Evoked responses appear to carry information about potential PSE. This result can be useful for screening patients for photosensitivity and it may also help to assess in a quantitative way the effectiveness of medical therapy.
Alkawadri, Rafeed; So, Norman K.; Van Ness, Paul C.; Alexopoulos, Andreas V.
IMPORTANCE The literature on cingulate gyrus epilepsy in the magnetic resonance imaging era is limited to case reports and small case series. To our knowledge, this is the largest study of surgically confirmed epilepsy arising from the anterior or posterior cingulate region. OBJECTIVE To characterize the clinical and electrophysiological findings of epilepsies arising from the anterior and posterior cingulate gyrus. DESIGN, SETTING, AND PARTICIPANTS We studied consecutive cingulate gyrus epilepsy cases identified retrospectively from the Cleveland Clinic and University of Texas Southwestern Medical Center epilepsy databases from 1992 to 2009. Participants included 14 consecutive cases of cingulate gyrus epilepsies confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. MAIN OUTCOMES AND MEASURES The main outcome measure was improvement in seizure frequency following surgery. The clinical, video electroencephalography, neuroimaging, pathology, and surgical outcome data were reviewed. RESULTS All 14 patients had cingulate epilepsy confirmed by restricted magnetic resonance image lesions and seizure freedom or marked improvement following lesionectomy. They were divided into 3 groups based on anatomical location of the lesion and corresponding seizure semiology. In the posterior cingulate group, all 4 patients had electroclinical findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a typical (Bancaud) group (6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or severe interictal personality changes) and an atypical group (4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less-favorable long-term surgical outcome). All atypical cases were associated with an underlying infiltrative astrocytoma. CONCLUSIONS AND RELEVANCE Posterior cingulate gyrus epilepsy may
Szabó, C. Ákos; Salinas, Felipe S; Narayana, Shalini
The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes. PMID:22276085
Umfleet, Laura Glass; Janecek, Julie K; Quasney, Erin; Sabsevitz, David S; Ryan, Joseph J; Binder, Jeffrey R; Swanson, Sara J
The sensitivity and specificity of the Selective Reminding Test (SRT) Delayed Recall, Wechsler Memory Scale (WMS) Logical Memory, the Boston Naming Test (BNT), and two nonverbal memory measures for detecting lateralized dysfunction in association with side of seizure focus was examined in a sample of 143 patients with left or right temporal-lobe epilepsy (TLE). Scores on the SRT and BNT were statistically significantly lower in the left TLE group compared with the right TLE group, whereas no group differences emerged on the Logical Memory subtest. No significant group differences were found with nonverbal memory measures. When the SRT and BNT were both entered as predictors in a logistic regression, the BNT, although significant, added minimal value to the model beyond the variance accounted for by the SRT Delayed Recall. Both variables emerged as significant predictors of side of seizure focus when entered into separate regressions. Sensitivity and specificity of the SRT and BNT ranged from 56% to 65%. The WMS Logical Memory and nonverbal memory measures were not significant predictors of the side of seizure focus.
Tashiro, Yuji; Sekito, Takeshi; Iwata, Takafumi; Yokoyama, Daishi; Nonaka, Toshiaki
We succeeded in development of SOG materials comprised of cage-type phenyl silsesquioxanes (PSQ) and their alkali soluble derivatives. The alkali soluble silsesquioxane (APSQ) can provide both positive and negative tone photosensitive SOG combination with diazo naphtoquinone (DNQ) and photo-base (acid) agent, respectively. Here we present feature of photolithography process and film properties for our SOG materials.
Resources - epilepsy ... The following organizations are good resources for information on epilepsy : Epilepsy Foundation -- www.epilepsy.com National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/ ...
Italiano, Domenico; Striano, Pasquale; Russo, Emilio; Leo, Antonio; Spina, Edoardo; Zara, Federico; Striano, Salvatore; Gambardella, Antonio; Labate, Angelo; Gasparini, Sara; Lamberti, Marco; De Sarro, Giovambattista; Aguglia, Umberto; Ferlazzo, Edoardo
Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies. References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies. Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in
Nanda, R N; Johnson, R H; Keogh, H J; Lambie, D G; Melville, I D
Clonazepam was added to the treatment of patients with poorly controlled epilepsy in a double-blind trial and an open trial. Considerable improvement occurred with patients with myoclonic jerks and tonic-clonic convulsions, and with photosensitive epilepsy. Patients with atypical petit mal and focal epilepsies also improved. Drowsiness was initially common but lasted only a short time. No evidence was found for an action of clonazepam on the metabolism of other drugs, but treatment with phenobarbitone lowered serum concentrations of clonazepam. We conclude that clonazepam is particularly valuable in epilepsy with associated myoclonsu and in photosensitive epilepsy. PMID:409803
Cunliffe, Vincent T; Baines, Richard A; Giachello, Carlo N G; Lin, Wei-Hsiang; Morgan, Alan; Reuber, Markus; Russell, Claire; Walker, Matthew C; Williams, Robin S B
This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. We consider recent discoveries made with each model organism and discuss the importance of these advances for the understanding and treatment of epilepsy in humans. The relative ease with which mutations in genes of interest can be produced and studied quickly and cheaply in these organisms, together with their anatomical and physiological simplicity in comparison to mammalian species, are major advantages when researchers are trying to unravel complex disease mechanisms. The short generation times of most of these model organisms also mean that they lend themselves particularly conveniently to the investigation of drug effects or epileptogenic processes across the lifecourse. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Ekenstedt, Kari J; Oberbauer, Anita M
Epilepsy is the most common neurologic disease in dogs and many forms are considered to have a genetic basis. In contrast, some seizure disorders are also heritable, but are not technically defined as epilepsy. Investigation of true canine epilepsies has uncovered genetic associations in some cases, however, many remain unexplained. Gene mutations have been described for 2 forms of canine epilepsy: primary epilepsy (PE) and progressive myoclonic epilepsies. To date, 9 genes have been described to underlie progressive myoclonic epilepsies in several dog breeds. Investigations into genetic PE have been less successful, with only 1 causative gene described. Genetic testing as an aid to diagnosis, prognosis, and breeding decisions is available for these 10 forms. Additional studies utilizing genome-wide tools have identified PE loci of interest; however, specific genetic tests are not yet developed. Many studies of dog breeds with PE have failed to identify genes or loci of interest, suggesting that, similar to what is seen in many human genetic epilepsies, inheritance is likely complex, involving several or many genes, and reflective of environmental interactions. An individual dog's response to therapeutic intervention for epilepsy may also be genetically complex. Although the field of inherited epilepsy has faced challenges, particularly with PE, newer technologies contribute to further advances. © 2013 Elsevier Inc. All rights reserved.
... Epilepsy Well Network The Managing Epilepsy Well (MEW) Network is a group of academic Prevention Research Centers that conduct studies related to epilepsy self-management. Read about MEW Network projects and how they are improving health and ...
Dodrill, Carl B.; Clemmons, David
Examined the validity of intellectual, neuropsychological, and emotional adjustment measures administered in high school in predicting vocational adjustment of 39 young adults with epilepsy. Results showed neuropsychological tests were the best predictors of later adjustment. Abilities were more related to final adjustment than variables…
Marsh, Eric D; Peltzer, Bradley; Brown, Merritt W; Wusthoff, Courtney; Storm, Phillip B; Litt, Brian; Porter, Brenda E
The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial electroencephalography (IEEG). Although ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure-onset location, although these studies were based upon relatively short EEG epochs. We employ a previously validated, computerized spike detector to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extratemporal lobe epilepsy. Approximately 8 h of IEEG, randomly selected 30-min segments of continuous interictal IEEG per patient, were analyzed over all intracranial electrode contacts. When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure-onset region in 11 of 19 patients. There was significant variability between individual 30-min segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low-voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure-onset region. Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori.
Marsh, Eric D.; Peltzer, Bradley; Brown, Merritt W.; Wusthoff, Courtney; Storm, Phillip B.; Litt, Brian; Porter, Brenda E.
Purpose The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial EEG (IEEG). While ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure onset location, though these studies were based upon relatively short EEG epochs. Methods We employ a previously validated, computerized spike detector, to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extra temporal lobe epilepsy. Approximately 8 hours of IEEG, randomly selected thirty-minute segments of continuous interictal IEEG per patient were analyzed over all intracranial electrode contacts. Results When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure onset region in 11 of 19 patients. There was significant variability between individual 30-minute segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure onset region. Conclusions Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori. PMID:19780794
Alkhamees, Hadeel A; Selai, Caroline E; Shorvon, Simon D; Kanner, Andres M
The aims of the current study were to translate and to validate the NDDI-E to the Arabic language to be used as a screening instrument to identify moderately severe symptoms of depression in people with epilepsy. The English version of the NDDI-E was translated to Arabic and back translated to English by two independent translators. A total of 51 patients, aged 18-56years old, with a diagnosis of epilepsy, completed the Arabic versions of the Beck Depression Inventory (BDI-II) and the NDDI-E. Patients with BDI scores >20 were considered to be suffering from moderately severe depressive symptoms. Cutoff scores, sensitivity, specificity, and positive and negative predictive values of the NDDI-E to identify symptomatic patients on the BDI were calculated. A sensitivity of 93.33% and a specificity of 94.44% were found with NDDI-E total scores >15. The positive predictive value was 87.5%, and the negative predictive value was 97.14%. Spearman's rank correlation between the BDI and the NDDI-E was high (r=.78, p=0.000, N=51). Internal consistency was at 0.926 (Cronbach's alpha). The Arabic version of the NDDI-E appears to be a reliable and sensitive instrument in the identification of moderately severe or severe depressive symptoms in people with epilepsy, and it can be used with all Arabic-speaking patients. Copyright © 2014 Elsevier Inc. All rights reserved.
Pandey, Ravindra K.; Shiau, Fuu-Yau; Meunier, Isabelle; Ramaprasad, Subbaraya; Sumlin, Adam B.; Dougherty, Thomas J.; Smith, Kevin M.
In order to evaluate the effect of substituents in photosensitizing activity, a series of long wavelength absorbing photosensitizers related to pyropheophorbides, bacteriopheophorbides, and benzoporphyrin derivatives were synthesized. Pheophorbide dimers, covalently joining two molecules of pyropheophorbide-a and bacteriopheophorbide-a with lysine as a cross-link were also prepared. The syntheses and spectroscopic properties of these compounds are discussed. Some of these compounds were tested for in vivo photosensitizing activity vis-a-vis Photofrin IITM, using the standard screening system of DBA/2 mice bearing transplanted SMT/F tumors. The preliminary in vivo results suggest that replacement of substituents at peripheral positions of the macrocycles causes a significant difference in photosensitizing efficacy.
Quinlan, Scott C; Cheng, Wendy Y; Ishihara, Lianna; Irizarry, Michael C; Holick, Crystal N; Duh, Mei Sheng
The aim of this study was to develop and validate an insurance claims-based algorithm for identifying urinary retention (UR) in epilepsy patients receiving antiepileptic drugs to facilitate safety monitoring. Data from the HealthCore Integrated Research Database(SM) in 2008-2011 (retrospective) and 2012-2013 (prospective) were used to identify epilepsy patients with UR. During the retrospective phase, three algorithms identified potential UR: (i) UR diagnosis code with a catheterization procedure code; (ii) UR diagnosis code alone; or (iii) diagnosis with UR-related symptoms. Medical records for 50 randomly selected patients satisfying ≥1 algorithm were reviewed by urologists to ascertain UR status. Positive predictive value (PPV) and 95% confidence intervals (CI) were calculated for the three component algorithms and the overall algorithm (defined as satisfying ≥1 component algorithms). Algorithms were refined using urologist review notes. In the prospective phase, the UR algorithm was refined using medical records for an additional 150 cases. In the retrospective phase, the PPV of the overall algorithm was 72.0% (95%CI: 57.5-83.8%). Algorithm 3 performed poorly and was dropped. Algorithm 1 was unchanged; urinary incontinence and cystitis were added as exclusionary diagnoses to Algorithm 2. The PPV for the modified overall algorithm was 89.2% (74.6-97.0%). In the prospective phase, the PPV for the modified overall algorithm was 76.0% (68.4-82.6%). Upon adding overactive bladder, nocturia and urinary frequency as exclusionary diagnoses, the PPV for the final overall algorithm was 81.9% (73.7-88.4%). The current UR algorithm yielded a PPV > 80% and could be used for more accurate identification of UR among epilepsy patients in a large claims database. Copyright © 2016 John Wiley & Sons, Ltd.
Li, Jinhua; Niu, Liyong; Zheng, Zijian; Yan, Feng
High performance photodetectors play important roles in the development of innovative technologies in many fields, including medicine, display and imaging, military, optical communication, environment monitoring, security check, scientific research and industrial processing control. Graphene, the most fascinating two-dimensional material, has demonstrated promising applications in various types of photodetectors from terahertz to ultraviolet, due to its ultrahigh carrier mobility and light absorption in broad wavelength range. Graphene field effect transistors are recognized as a type of excellent transducers for photodetection thanks to the inherent amplification function of the transistors, the feasibility of miniaturization and the unique properties of graphene. In this review, we will introduce the applications of graphene transistors as photodetectors in different wavelength ranges including terahertz, infrared, visible, and ultraviolet, focusing on the device design, physics and photosensitive performance. Since the device properties are closely related to the quality of graphene, the devices based on graphene prepared with different methods will be addressed separately with a view to demonstrating more clearly their advantages and shortcomings in practical applications. It is expected that highly sensitive photodetectors based on graphene transistors will find important applications in many emerging areas especially flexible, wearable, printable or transparent electronics and high frequency communications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Muñana, Karen R
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.
Franceschetti, Silvana; Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico
To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.
Haenisch, Sierk; Zhao, Yi; Chhibber, Aparna; Kaiboriboon, Kitti; Do, Lynn V; Vogelgesang, Silke; Barbaro, Nicholas M; Alldredge, Brian K; Lowenstein, Daniel H; Cascorbi, Ingolf; Kroetz, Deanna L
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural
Carbon nanotubes (CNTs) photosensitize the production of reactive oxygen species that can damage organisms by biomembrane oxidation or mediate CNTs' environmental transformations. The photosensitized nature of derivatized carbon nanotubes from various synthetic methods, and thus ...
Malhotra, S; Malhotra, S; Fernandes, P; Ghosh, D
A case of child with gelastic epilepsy following administration of antirabies vaccine is presented. No associated structural brain could be identified in the patient. Possibility of relationship between antirables vaccine and gelastic epilepsy is discussed.
Ramocki, Melissa B.; Bartnik, Magdalena; Szafranski, Przemyslaw; Kołodziejska, Katarzyna E.; Xia, Zhilian; Bravo, Jaclyn; Miller, G. Steve; Rodriguez, Diana L.; Williams, Charles A.; Bader, Patricia I.; Szczepanik, Elżbieta; Mazurczak, Tomasz; Antczak-Marach, Dorota; Coldwell, James G.; Akman, Cigdem I.; McAlmon, Karen; Cohen, Melinda P.; McGrath, James; Roeder, Elizabeth; Mueller, Jennifer; Kang, Sung-Hae L.; Bacino, Carlos A.; Patel, Ankita; Bocian, Ewa; Shaw, Chad A.; Cheung, Sau Wai; Mazurczak, Tadeusz; Stankiewicz, Paweł
We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180–500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1−/−) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function. PMID:21109226
Ramocki, Melissa B; Bartnik, Magdalena; Szafranski, Przemyslaw; Kołodziejska, Katarzyna E; Xia, Zhilian; Bravo, Jaclyn; Miller, G Steve; Rodriguez, Diana L; Williams, Charles A; Bader, Patricia I; Szczepanik, Elżbieta; Mazurczak, Tomasz; Antczak-Marach, Dorota; Coldwell, James G; Akman, Cigdem I; McAlmon, Karen; Cohen, Melinda P; McGrath, James; Roeder, Elizabeth; Mueller, Jennifer; Kang, Sung-Hae L; Bacino, Carlos A; Patel, Ankita; Bocian, Ewa; Shaw, Chad A; Cheung, Sau Wai; Mazurczak, Tadeusz; Stankiewicz, Paweł
We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180-500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1⁻(/)⁻) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function. Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Reports on adverse drug reactions, as they were recorded at the Norwegian Medicines Control Authority beginning in the year 1970 up to 1994 were analyzed especially with regard to cutaneous reactions and photosensitivity reactions. During the time period, almost 13.000 side effects were reported. Out of these 799 reports involved the skin and appendages, and 64 out of these reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs which most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the background of experimental data and the prescription rates of these substances.
Dougherty, Thomas J.; Pandey, R. K.; Nava, Hector R.; Smith, Judy L.; Douglass, Harold O.; Edge, Stephen B.; Bellnier, David A.; O'Malley, Linda; Cooper, Michele
The hexyl ether derivative or HPPH, has been identified as an optimal active in vivo photosensitizer in pre-clinical studies and has been evaluated clinically in obstructive esophageal cancer in five patients to date. The photosensitizer appears to have no systemic toxicity and be effective at low drug and light doses. Further, cutaneous photosensitivity appears to persist only 5-7 days.
Masnou, P; Nahum-Moscovoci, L
Video games may induce epileptic seizures in some subjects. Most of them have photosensitive epilepsy. The triggering factors are multiple: characteristics of the softwares, effects of the electronic screen and interactivity. The wide diffusion of the video games explain the large number of descriptions of videogame induced seizures. Historical aspects and an analysis of the underlying mechanisms of videogame induced seizures are presented.
Miller, John W.; Hakimian, Shahin
Purpose of Review: This article outlines indications for neurosurgical treatment of epilepsy, describes the presurgical workup, summarizes surgical approaches, and details expected risks and benefits. Recent Findings: There is class I evidence for the efficacy of temporal lobectomy in treating intractable seizures, and accumulating documentation that successful surgical treatment reverses much of the disability, morbidity, and excess mortality of chronic epilepsy. Summary: Chronic, uncontrolled focal epilepsy causes progressive disability and increased mortality, but these can be reversed with seizure control. Vigorous efforts to stop seizures are warranted. If two well-chosen and tolerated medication trials do not achieve seizure control, an early workup for epilepsy surgery should be arranged. If this workup definitively identifies the brain region from which the seizures arise, and this region can be removed with a low risk of disabling neurologic deficits, neurosurgery will have a much better chance of stopping seizures than further medication trials. PMID:23739107
Zifkin, B G; Kasteleijn-Nolst Trenité, D
Reflex epilepsy of the visual system is charecterised by seizures precipitated by visual stimuli. EEG responses to intermittent photic stimulation depend on the age and sex of the subject and on how stimulation is performed: abnormalities are commonest in children and adolescents, especially girls. Only generalised paroxysmal epileptiform discharges are clearly linked to epilepsy. Abnormal responses may occur in asymptomatic subjects, especially children. Photosensitivity has an important genetic component. Some patients are sensitive to patterns, suggesting an occipital trigger for these events. Myoclonus and generalised convulsive and nonconvulsive seizures may be triggered by visual stimuli. Partial seizures occur less often and can be confused with migraine. Although usually idiopathic, photosensitive epilepsy may occur in degenerative diseases and some patients with photosensitive partial seizures have brain lesions. Sunlight and video screens, including television, video games, and computer displays, are the commonest environmental triggers of photosensitive seizures. Outbreaks of triggered seizures have occurred when certain flashing or patterned images have been broadcast. There are regulations to prevent this in some countries only. Pure photosensitive epilepsy has a good prognosis. There is a role for treatment with and without antiepileptic drugs, but photosensitivity usually does not disappear spontaneously, and then typically in the third decade.
Afawi, Zaid; Oliver, Karen L.; Kivity, Sara; Mazarib, Aziz; Blatt, Ilan; Neufeld, Miriam Y.; Helbig, Katherine L.; Goldberg-Stern, Hadassa; Misk, Adel J.; Straussberg, Rachel; Walid, Simri; Mahajnah, Muhammad; Lerman-Sagie, Tally; Ben-Zeev, Bruria; Kahana, Esther; Masalha, Rafik; Kramer, Uri; Ekstein, Dana; Shorer, Zamir; Wallace, Robyn H.; Mangelsdorf, Marie; MacPherson, James N.; Carvill, Gemma L.; Mefford, Heather C.; Jackson, Graeme D.; Scheffer, Ingrid E.; Bahlo, Melanie; Gecz, Jozef; Heron, Sarah E.; Corbett, Mark; Mulley, John C.; Dibbens, Leanne M.; Korczyn, Amos D.
Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID:26802095
Golub, M. A.
The photosensitized oxidation or singlet oxygenation of unsaturated hydrocarbon polymers and of their model compounds was reviewed. Emphasis was on cis and trans forms of 1,4-polyisoprene, 1,4-polybutadiene and 1,2-poly(1,4-hexadiene), and on 1,4-poly(2,3-dimethyl-1,3-butadiene). The microstructural changes which occur in these polymers on reaction with O2-1 in solution were investigated by infrared H-1 and C-13 NMR spectroscopy. The polymers were shown to yield allylic hydroperoxides with shifted double bonds according to the ene mechanism established for simple olefins. The photosensitized oxidation of the above unsaturated polymer exhibited zero order kinetics, the relative rates paralleling the reactivities of the corresponding simple olefins towards O2-1.
Elkeeb, Dena; Elkeeb, Laila; Maibach, Howard
The level of interest in photoirritation (phototoxicity) has increased because of the awareness among the scientific community of the increase in the UV portion of the solar spectrum reaching the earth. The need of new chemicals and drugs puts pressure on pre-test methods for side effects, especially interactive adverse effects with UV light. So pre-marketing clinical trials conducted before a new drug is licensed are essential, as such, at the early phases of the discovery process of the drug/chemical, developing an efficacious photosensitivity testing system is prudent to avoid such potential side effects. To review published literature and provide an overview on exogenous photosensitivity and assays used to evaluate the photosensitivity potential of drugs/chemicals. As well as testing considerations by the Regulatory bodies (namely, the Organization for Economic Cooperation and Development, the U.S Food and Drug Administration and the European Union regulatory agencies). We searched medical and scientific search engines as well as websites of the EU and US Regulatory agencies and used keywords such as cutaneous phototoxicity, phototoxicity in vitro assays, phototoxicity in vivo assays and other related terms.
Desguerre, I; Hully, M; Rio, M; Nabbout, R
Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis. Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy. Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Murdock, Matthew C.; Morgan, Joseph A.; Laverghetta, Thomas S.
The teacher-student relationship can afford the music educator an opportunity to be the first to identify behaviors associated with epilepsy. A case of a student with epilepsy, based on the authors' experience, is described in which the music educators were the first and only individuals to become aware of a change in the student's behavior, after…
... abilities of people with epilepsy, fear seizures, or lack knowledge about seizure first aid or are not comfortable ... they help eliminate barriers to care, such as lack of transportation or ... both English- and Spanish-speaking adults with epilepsy. Researchers are ...
Barnes Heller, Heidi
Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy. Copyright © 2017 Elsevier Inc. All rights reserved.
Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford
Objective: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. Methods: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Results: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20–62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive “fogginess” (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. Conclusions: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. ClinicalTrials.gov identifier: NCT02178995. Classification of evidence: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. PMID:28031390
... or antiepileptic drugs), may reduce the number of future seizures: These drugs are taken by mouth. Which ... 23986299 . Wiebe S. The epilepsies. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ...
... time pass. Go back to the top About Pre-surgical Evaluation for Epilepsy Many patients have similar questions about having seizure surgery and what tests may be needed before surgery. The following general ...
Cendes, Fernando; Theodore, William H.; Brinkmann, Benjamin H.; Sulc, Vlastimil; Cascino, Gregory D.
Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454
Baca, Christine B.; Loddenkemper, Tobias; Vickrey, Barbara G.; Dlugos, Dennis
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
Bakaki, Paul M.; Koroukian, Siran M.; Jackson, Leila W.; Albert, Jeffrey M.; Kaiboriboon, Kitti
Purpose To determine the minimum enrollment duration for identifying incident cases of epilepsy in administrative data. Methods We performed a retrospective dynamic cohort study using Ohio Medicaid data from 1992–2006 to identify a total of 5,037 incident epilepsy cases who had at least 1 year of follow-up prior to epilepsy diagnosis (epilepsy-free interval). The incidence for epilepsy-free intervals from 1 to 8 years, overall and stratified by pre-existing disability status, was examined. The graphical approach between the slopes of incidence estimates and the epilepsy-free intervals was used to identify the minimum epilepsy-free interval that minimized misclassification of prevalent as incident epilepsy cases. Results As the length of epilepsy-free interval increased, the incidence rates decreased. A graphical plot showed that the decline in incidence of epilepsy became nearly flat beyond the third epilepsy-free interval. Conclusion The minimum of 3-year epilepsy-free interval is needed to differentiate incident from prevalent cases in administrative data. Shorter or longer epilepsy-free intervals could result in over- or under-estimation of epilepsy incidence. PMID:23791310
Golding, Paul S.; Maddocks, L.; King, Terence A.; Drucker, D. B.
Photosensitization and inactivation efficacy of three bacterial species: Prevotella nigrescens, Staphylococcus aureus and Escherichia coli have been investigated. Samples of Staphylococcus aureus and Escherichia coli were treated with the triphenylmethane dye malachite green isothiocyanate and exposed to light from a variety of continuous and pulsed light sauces at a wavelength of approximately 630 nm. Inactivation of the Gram-positive species Staphylococcus aureus was found to increase with radiation dose, whilst Gram-negative Escherichia coli was resistant to such treatment. Samples of the pigmented species Prevotella nigrescens were found to be inactivated by exposure to light alone. The mechanism of photosensitization and inactivation of Staphylococcus aureus with malachite green isothiocyanate is addressed. The possible roles of the excited triplet state of the photosensitizer, the involvement of molecular oxygen, and the bacterial cell wall are discussed. Photosensitization may provide a way of eliminating naturally pigmented species responsible for a variety of infections, including oral diseases such as gingivitis and periodontitis.
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
Hirsch, E; de Saint-Martin, A; Arzimanoglou, A
The diagnosis, treatment, and prognosis of seizure disorders depend on the correct identification of epileptic syndromes. Partial epilepsies are heterogeneous and can be divided into idiopathic, cryptogenic, and symptomatic epilepsies. The most common of the idiopathic localization-related epilepsies is benign epilepsy with rolandic or centrotemporal spikes (BECTS). Seizures remain rare and the use of antiepileptic drug (AED) treatment in all patients does not appear justified. Children who present with some of the electroclinical characteristics of BECTS may also display severe unusual neurologic, neuropsychological, or atypical symptoms. In some cases, carbamazepine has been implicated as a triggering factor. Primary reading epilepsy and idiopathic occipital lobe epilepsies with photosensitivity are examples of an overlap between idiopathic localization-related and generalized epilepsies and respond well to sodium valproate. Autosomal dominant nocturnal frontal lobe epilepsy and benign familial infantile convulsions are recently described syndromes, differing in several ways from classical idiopathic localization-related epileptic syndromes. In cryptogenic or symptomatic epilepsy, the topography of the epileptogenic zone might influence drug efficacy. An individualized approach to AED selection, tailored to each patient's needs, should be used. Resistance of seizures to antiepileptic therapy may be due to diagnostic and/or treatment error or may be the result of noncompliance. Increasing the dosage, discontinuation or replacement of a drug, or addition of a second drug is indicated in truly resistant cases. The use of more than two AEDs rarely optimizes seizure control, and in some cases reduction of treatment may improve seizure control while lessening side effects. EEG-video assessment of patients with refractory epilepsy is important. Indications for and timing of epilepsy surgery should be reconsidered. Surgical therapy should probably be used more often and
Abrahamse, Heidi; Hamblin, Michael R.
Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. PMID:26862179
Abrahamse, Heidi; Hamblin, Michael R
Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. © 2016 Authors; published by Portland Press Limited.
Millson, Charles E.; Wilson, Michael; MacRobert, Alexander J.; Thurrell, Wendy; Mlkvy, Peter; Davies, Claire; Bown, Stephen G.
Helicobacter pylori (H. pylori) is associated with a large number of gastroduodenal disorders. Clearance of the bacteria has been shown to benefit patients with duodenal ulcers, gastric ulcers, and certain rare types of gastric tumors. Broad-spectrum antibiotics are the mainstay of current treatment strategies but side-effects, poor compliance, and drug resistance limit their usefulness. We sensitized H. pylori with toluidine blue, haematoporphyrin derivative, aluminum disulphonated phthalocyanine, methylene blue or protoporphyrin IX prior to exposure to low-power laser light from either a gallium aluminum arsenide laser or a helium neon gas laser. All 5 sensitizers caused reductions of greater than 1000-fold in the number of viable bacteria. Light alone had no effect and only HpD caused a significant decrease in bacterial numbers without laser light. Next, we sensitized H. mustelae on explanted ferret gastric mucosa (ex vivo) with the same sensitizers and exposed them to light from a copper vapor pumped dye laser tuned appropriately. MB caused significant reductions in bacterial counts. Successful lethal photosensitization of Helicobacter pylori both in vitro and ex vivo raises the possibility of a local method for eradicating the bacteria, especially as the bacteria are only found in those parts of the upper gastrointestinal tract that are accessible to the endoscope.
Do, Michael Tri Hoang; Yau, King-Wai
Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar "image vision," in that the basic information is light or darkness over time, independent of spatial patterns. "Nonimage" vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.
Serafini, Anna; Lukas, Rimas V; VanHaerents, Stephen; Warnke, Peter; Tao, James X; Rose, Sandra; Wu, Shasha
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.
Houle, Jean-Marie; Strong, H Andrew
Verteporfin (Visudyne, Novartis AG) is a light-activated drug that reduces the risk of vision loss in patients with certain types of choroidal neovascularization (CNV). Because photosensitivity can occur with photosensitizers, it is important for ophthalmologists providing verteporfin therapy to understand its time course and duration, as well as the incidence of photosensitivity reactions. Data were obtained from three sources: 1) the time course of skin photosensitivity in 17 volunteers by measuring erythema/edema over time after verteporfin, using red light exposure; 2) the duration of skin photosensitivity in 30 patients with skin cancer by exposing skin to simulated solar light and calculating the daily minimal erythematous dose; and 3) the incidences of photosensitivity reactions as recorded in three phase III trials in patients with CNV secondary to age-related macular degeneration or pathologic myopia who received the regimen of verteporfin therapy currently approved by regulatory authorities (infusion of 6 mg/m(2) body surface area). 1) Skin photosensitivity was high at the first timepoint of 1.5 hours after dosing and decreased rapidly thereafter; 2) the duration of skin photosensitivity was dose dependent, ranging from 2.0 to 6.7 days at 6 to 20 mg/m(2), respectively (mean of 2 days at a dose of 6 mg/m(2)); and 3) photosensitivity reactions occurred in only 2.2% of patients in the phase III trials, including two severe events, one secondary to extravasation. All treatment-related reactions in the phase III trials occurred within the first 2 days after dosing, with the exception of two mild reactions and one moderate reaction that occurred 3 days after treatment. Verteporfin is associated with short-lived photosensitivity and a low incidence of photosensitivity reactions in clinical trials, most of which could probably have been avoided by adherence to protocol instructions for skin protection.
Sidhu, Meneka Kaur; Duncan, John S; Sander, Josemir W
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.
Hussain, Syeda M; Herling, Valdo Rodrigues; Rodrigues, Paulo Henrique Mazza; Naz, Ishrat; Khan, Hamayun; Khan, Muhammad Tahir
Photosensitization is severe dermatitis or oxidative/chemical changes in the epidermal tissues activated by the light-induced excitation of molecules within the tissue. It is a series of reactions mediated through light receptors and is more common when the plant-produced metabolites are heterocyclic/polyphenols in nature. The areas affected are exposed body parts and mostly non-pigmented areas with least ultraviolet protection. Similarly, cellular alteration also occurs in the affected animal's dermal tissues and body parts and grazing animals by the accumulation and activation of photodynamic molecules. Photo-oxidation can also occur within the plant due to the generation of reactive oxygen species causing damage and degradation in the form of free radicals and DNA. During the last few decades, many new tropical grass species have been introduced in the grazing lands which are genetically modified, and the animals grazing on them are facing various forms of toxicity including photosensitization. The plant's secondary metabolites/drugs may cause toxicity when bacteria, viral agents, fungi (Pithomyces chartarum), or neoplasia injures the liver and prevents the phylloerythrin excretion. All these may disturb the liver enzymes and blood profile causing a decrease in weight and production (wool and milk etc.) with severe dermal, digestive, and nervous problems. Recent advancements in OMICS (cellomics, ethomics, metabolomics, metabonomics, and glycomics) have enabled us to detect and identify the plants' secondary metabolites and changes in the animal's physiology and histopathology as a causative of photosensitivity. The review focuses on types of photosensitization, reasons, secondary metabolic compounds, chemistry, and environmental effect on plants.
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Reddy, Doodipala Samba; Volkmer, Randy
Aside from brain injury and genetic causes, there is emerging information on brain infection and inflammation as a common cause of epilepsy. Neurocysticercosis (NCC), the most common cause of epilepsy worldwide, is caused by brain cysts from the Taenia solium tapeworm. In this article, we provide a critical analysis of current and emerging information on the relationship between NCC infection and epilepsy occurrence. We searched PubMed and other databases for reports on the prevalence of NCC and incidence of epilepsy in certain regions worldwide. NCC is caused by brain cysts from the T. solium and related tapeworms. Many people with NCC infection may develop epilepsy but the rates are highly variable. MRI imaging shows many changes including localization of cysts as well as the host response to treatment. Epilepsy, in a subset of NCC patients, appears to be due to hippocampal sclerosis. Serologic and brain imaging profiles are likely diagnostic biomarkers of NCC infection and are also used to monitor the course of treatments. Limited access to these tools is a key limitation to identify and treat NCC-related epilepsy in places with high prevalence of this parasite infestation. Overall, NCC is a common infection in many patients with epilepsy worldwide. Additional clinical and animal studies could confirm common pathology of NCC as a postinfectious epilepsy that is curable. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Ramaratnam, S; Baker, G A; Goldstein, L
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, electroencephalogram (EEG) bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group trial register (11 June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 2, 2003), MEDLINE (on 11 June 2003) and cross references from identified publications. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions
Henning, Oliver J; Nakken, Karl O; Træen, Bente; Mowinckel, Petter; Lossius, Morten
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.
Ogawa, Emiyu; Takahashi, Mei; Arai, Tsunenori
To quantitatively investigate photosensitization reaction in vitro against myocardial cells with photosensitizer rich condition in solution using Talaporfin sodium in the well of a 96 well plate, we studied photosensitization reaction progress in this well. We have proposed non-thermal conduction block of myocardium tissue using the photosensitization reaction with laser irradiation shortly after Talaporfin sodium injection. In above situation, the photosensitizer is located outside the myocardial cells in high concentration. To understand interaction of the photosensitization reaction in which the photosensitizer distributes outside cells, the photosensitization reaction progress in the well was studied. Talaporfin sodium (799.69 MW) solution and a 663 nm diode laser were used. The photosensitizer solution concentrations of 12.5-37.5 μM were employed. The photosensitizer fluorescence with 0.29 W/cm2 in irradiance, which was optimized in previous cell death study, was measured during the laser irradiation until 40 J/cm2. The photosensitizer solution absorbance and dissolved oxygen pressure after the laser irradiation were also measured. We found that the photosensitization reaction progress had 2 distinctive phases of different reaction rate: rapid photosensitization reaction consuming dissolved oxygen and gentle photosensitization reaction with oxygen diffusion from the solution-air boundary. The dissolved oxygen pressure and photosensitizer solution absorbance were 30% and 80% of the initial values after the laser irradiation, respectively. Therefore, oxygen was rate-controlling factor of the photosensitization reaction in the well with the photosensitizer rich condition. In the oxygen diffusion phase, the oxygen pressure was maintained around 40 mmHg until the laser irradiation of 40 J/cm2 and it is similar to that of myocardium tissue in vivo. We think that our 96 well plate in vitro system may simulate PDT in myocardial tissue with photosensitization reaction
Leu, Costin; de Kovel, Carolien G F; Zara, Federico; Striano, Pasquale; Pezzella, Marianna; Robbiano, Angela; Bianchi, Amedeo; Bisulli, Francesca; Coppola, Antonietta; Giallonardo, Anna Teresa; Beccaria, Francesca; Trenité, Dorothée Kasteleijn-Nolst; Lindhout, Dick; Gaus, Verena; Schmitz, Bettina; Janz, Dieter; Weber, Yvonne G; Becker, Felicitas; Lerche, Holger; Kleefuss-Lie, Ailing A; Hallman, Kerstin; Kunz, Wolfram S; Elger, Christian E; Muhle, Hiltrud; Stephani, Ulrich; Møller, Rikke S; Hjalgrim, Helle; Mullen, Saul; Scheffer, Ingrid E; Berkovic, Samuel F; Everett, Kate V; Gardiner, Mark R; Marini, Carla; Guerrini, Renzo; Lehesjoki, Anna-Elina; Siren, Auli; Nabbout, Rima; Baulac, Stephanie; Leguern, Eric; Serratosa, Jose M; Rosenow, Felix; Feucht, Martha; Unterberger, Iris; Covanis, Athanasios; Suls, Arvid; Weckhuysen, Sarah; Kaneva, Radka; Caglayan, Hande; Turkdogan, Dilsad; Baykan, Betul; Bebek, Nerses; Ozbek, Ugur; Hempelmann, Anne; Schulz, Herbert; Rüschendorf, Franz; Trucks, Holger; Nürnberg, Peter; Avanzini, Giuliano; Koeleman, Bobby P C; Sander, Thomas
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31
Seker Yilmaz, Berna; Okuyaz, Cetin; Komur, Mustafa
Our study sought to identify early predictive factors of medically intractable childhood epilepsy. A cohort of epileptic children from the city of Mersin was retrospectively investigated. All patients received care from the same Department of Pediatric Neurology. The epileptic cohort was divided into a drug-responsive epilepsy group and an intractable epilepsy group. Intractable epilepsy is defined as continued seizures in children despite adequate therapy with two or more antiepileptic drugs for more than 18 months. Strong univariate association was observed between intractability and several factors: age of onset, high initial seizure frequency, symptomatic etiology, mixed seizure types, previous history of status epilepticus, febrile and neonatal seizures, mental and motor developmental delay, multiple seizures in 1 day, electroencephalogram abnormalities, magnetic resonance imaging findings, and specific epileptic syndromes. Logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy. We suggest that medical intractability in childhood epilepsy can be predicted by monitoring these factors. Along with early prediction, alternative therapies may be designed to provide patients better seizure control and quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.
Rajagopalan, Raghavan; Karwa, Amolkumar; Poreddy, Amruta R.; Lusiak, Przemyslaw M.; Pandurangi, Raghoottama S.; Cantrell, Gary L.; Dorshow, Richard B.
Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation with visible light were prepared and tested for cell viability using U397 leukemia cell line. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light.
Cramer, Joyce A; Wang, Zhixiao J; Chang, Eunice; Powers, Annette; Copher, Ronda; Cherepanov, Dasha; Broder, Michael S
Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had ≥1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and
Pulido Fontes, L; Quesada Jimenez, P; Mendioroz Iriarte, M
Epigenetics is the study of heritable modifications in gene expression that do not change the DNA nucleotide sequence. Some of the most thoroughly studied epigenetic mechanisms at present are DNA methylation, post-transcriptional modifications of histones, and the effect of non-coding RNA molecules. Gene expression is regulated by means of these mechanisms and disruption of these molecular pathways may elicit development of diseases. We describe the main epigenetic regulatory mechanisms and review the most recent literature about epigenetic mechanisms and how those mechanisms are involved in different epileptic syndromes. Identifying the epigenetic mechanisms involved in epilepsy is a promising line of research that will deliver more in-depth knowledge of epilepsy pathophysiology and treatments. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
Whitchurch, Ashwin K.; Ashok, B. H.; Kumaar, Raman V.; Sarukesi, K.; Jose, K. A.; Varadan, Vijay K.
Epilepsy is a form of brain disorder caused by abnormal discharges of neurons. The most common manifestations of epilepsy are seizures which could affect visual, aural and motor abilities of a person. Absence epilepsy is a form of epilepsy common mostly in children. The most common manifestations of absence epilepsy are staring and transient loss of responsiveness. Also, subtle motor activities may occur. Due to the subtle nature of these symptoms, episodes of absence epilepsy may often go unrecognized for long periods of time or be mistakenly attributed to attention deficit disorder or daydreaming. Spells of absence epilepsy may last about 10 seconds and occur hundreds of times each day. Patients have no recollections of the events occurred during those seizures and will resume normal activity without any postictal symptoms. The EEG during such episodes of Absence epilepsy shows intermittent activity of 3 Hz generalized spike and wave complexes. As EEG is the only way of detecting such symptoms, it is required to monitor the EEG of the patient for a long time, usually the whole day. This requires that the patient be connected to the EEG recorder all the time and thus remain only in the bed. So, effectively the EEG is being monitored only when the patient is stationary. The wireless monitoring system described in this paper aims at eliminating this constraint and enables the physician to monitor the EEG when the patient resumes his normal activities. This approach could even help the doctor identify possible triggers of absence epilepsy.
Ramaratnam, S; Baker, G A; Goldstein, L
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, EEG bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE using OVID (1966 - May 2001) and cross references from identified publications. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for patients with epilepsy. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency, and quality of life. We found three small trials (50 patients) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and two of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in subjects with greatest seizure reduction. Educational interventions were found to be beneficial in improving the
Smart, Otis; Burrell, Lauren
Pattern classification for intracranial electroencephalogram (iEEG) and functional magnetic resonance imaging (fMRI) signals has furthered epilepsy research toward understanding the origin of epileptic seizures and localizing dysfunctional brain tissue for treatment. Prior research has demonstrated that implicitly selecting features with a genetic programming (GP) algorithm more effectively determined the proper features to discern biomarker and non-biomarker interictal iEEG and fMRI activity than conventional feature selection approaches. However for each the iEEG and fMRI modalities, it is still uncertain whether the stochastic properties of indirect feature selection with a GP yield (a) consistent results within a patient data set and (b) features that are specific or universal across multiple patient data sets. We examined the reproducibility of implicitly selecting features to classify interictal activity using a GP algorithm by performing several selection trials and subsequent frequent itemset mining (FIM) for separate iEEG and fMRI epilepsy patient data. We observed within-subject consistency and across-subject variability with some small similarity for selected features, indicating a clear need for patient-specific features and possible need for patient-specific feature selection or/and classification. For the fMRI, using nearest-neighbor classification and 30 GP generations, we obtained over 60% median sensitivity and over 60% median selectivity. For the iEEG, using nearest-neighbor classification and 30 GP generations, we obtained over 65% median sensitivity and over 65% median selectivity except one patient. PMID:25580059
Drapak, Stepan I.; Orletskii, Volodymyr B.; Bahtinov, Anatolii P.; Kovalyuk, Zakhar D.; Fotiy, Vasyl D.
Room temperature photosensitivity and its spectral distribution are investigated for a hetercontact between a layered semiconductor (p-InSe) and a biological entity (propolis). The obtained heterocontacts has a maximum photosensitivity >= 10^4 V/W. It is shown that the form of spectral sensitivity curve depends on the way of the heterocontact preparation. The long-wave edge of relative quantum efficiency varies from hν =1.2 eV (the energy gap for InSe at T=300 K) to 1.6 eV depending on a state of aggregation of propolis. The maximum photosensitivity in the long-wave spectral range takes place when the propolis layer is under illumination. The obtained peculiarities of the photoelectrical properties cannot be explained in the framework of the classical description of photosensitivity spectral description (the window effect) what follows from the optical absorption measurements for InSe and propolis in the range hν <= 1.2 eV. Impurity states in the energy gap of InSe and states at the heterocontact interface (a classical case of isotype p-p heterojunction) also do not give an appropriate explanation. To interpret the obtained results the complexity of the chemical composition of propolis, a product from honey bee, must be taken into account.
de Lijser, H J Peter; Fardoun, Fadia H; Sawyer, Jody R; Quant, Michelle
[reaction: see text] Deprotection of oximes to their corresponding carbonyl compounds through the use of photosensitized electron-transfer reactions proceeds in reasonable to good yields. Better yields are obtained in nonpolar solvents and when triplet sensitizers are used. Preliminary mechanistic studies suggest the involvement of an iminoxyl radical.
Köhling, Rüdiger; Wolfart, Jakob
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
Matroule, J Y; Carthy, C M; Granville, D J; Jolois, O; Hunt, D W; Piette, J
Pyropheophorbide-a methylester (PPME) is a second generation of photosensitizers used in photodynamic therapy (PDT). We demonstrated that PPME photosensitization triggered apoptosis of colon cancer cells as measured by using several classical parameters such as DNA laddering, PARP cleavage, caspase activation and mitochondrial release of cytochrome c. Preincubation of cells with N-acetyl cysteine (NAC) or pyrolidine dithiocarbamate (PDTC) protected against apoptosis mediated by PPME photosensitization showing that reactive oxygen species (ROS) are involved as second messengers. On the other hand, photosensitization carried out in the presence of deuterium oxide (D2O) which enhances singlet oxygen (1O2) lifetime only increases necrosis without affecting apoptosis. Since PPME was localized in the endoplasmic reticulum (ER)/Golgi system and lysosomes, other messengers than ROS were tested such as calcium, Bid, Bap31, phosphorylated Bcl-2 and caspase-12 but none was clearly identified as being involved in triggering cytochrome c release from mitochondria. On the other hand, we demonstrated that the transduction pathways leading to NF-kappaB activation and apoptosis were clearly independent although NF-kappaB was shown to counteract apoptosis mediated by PPME photosensitization.
Kurth, Tobias; Lewis, Barbara E; Walker, Alexander M
To evaluate health care resource utilization (HRU) in active epilepsy. Thomson-Reuters insurance databases included 14 million persons in 2005-2007. We extracted information for individuals with insurance claims suggestive of epilepsy. Using iterative expert classification, we sorted patients by type of epilepsy. For each type we calculated prevalence and HRU. A distance analysis identified closely similar types, and a principal components analysis revealed dimensions of variation in HRU. The prevalence of active epilepsy was 3.4 per 1,000. Most common diagnoses among 46,847 patients were generalized convulsive epilepsy (33.3%) and complex partial seizures (24.8%). Patients averaged 10 physician visits per year, 24 diagnostic tests/procedures per year, >30 drug dispensings per year, and <1 emergency room (ER) visit per year, the minority of each of these being related to epilepsy. Female patients generally had more HRU, and HRU increased with age. Patients were hospitalized most frequently for disorders other than epilepsy. HRU was similar for most epilepsy types, excepting grand mal status, epilepsia partialis continua, and infantile spasms. The first principal components of HRU variation was nonepilepsy HRU, followed by components of epilepsy-related medications, other epilepsy/emergency care, and epilepsy visits/diagnostic procedures. The prevalence of active epilepsy in the United States is substantially less than the prevalence of any history of recurrent seizure. Nonepilepsy-related HRU dominated HRU in epilepsy patients and was the principal source of variation. There is a core set of epilepsy diagnoses, the HRU patterns of which are indistinguishable, whereas patients with grand mal status, epilepsia partialis continua, and infantile spasms all have distinct patterns. To provide more specific insights into the economic impact of the condition, studies of HRU in epilepsy should make a distinction about epilepsy-related and unrelated care.
Jin, Guorui; Prabhakaran, Molamma P; Kai, Dan; Kotaki, Masaya; Ramakrishna, Seeram
Poly(3-hexylthiophene) (P3HT) is one of the most promising photovoltaic (PV) polymers in photocurrent therapy. A novel photosensitive scaffold for skin tissue engineering was fabricated by blending P3HT with polycaprolactone (PCL) and electrospun to obtain composite PCL/P3HT nanofibers with three different weight ratios of PCL : P3HT (w/w) of 150 : 2 [PCL/P3HT(2)], 150 : 10 [PCL/P3HT(10)] and 150 : 20 [PCL/P3HT(20)]. The photosensitive properties of the blend solutions and the composite nanofibers of PCL/P3HT were investigated. The incident photon-to-electron conversion efficiencies of the PCL/P3HT(2), PCL/P3HT(10), PCL/P3HT(20) were identified as 2.0 × 10(-6), 1.6 × 10(-5) and 2.9 × 10(-5), respectively, which confirm the photosensitive ability of the P3HT-containing scaffolds. The biocompatibility of the scaffold was evaluated by culturing human dermal fibroblasts and the results showed that the proliferation of HDFs under light stimulation on PCL/P3HT(10) was 12.8%, 11.9%, and 11.6% (p ≤ 0.05) higher than the cell growth on PCL, PCL/P3HT(2) and PCL/P3HT(20), respectively. Human dermal fibroblasts cultured under light stimulation on PCL/P3HT(10) not only showed better cell proliferation but also retained cell morphology similar to the phenotype observed on tissue culture plates (control). Our experimental results suggest novel and potential application of an optimized amount of P3HT-containing scaffold, especially PCL/P3HT(10) nanofibrous scaffold in photocurrent therapy for skin regeneration.
Brozek-Pluska, B; Kopec, M
Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. Copyright © 2016 Elsevier B.V. All rights reserved.
Brozek-Pluska, B.; Kopec, M.
Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin (Hp) in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy (PDT), photodynamic diagnosis (PDD) and photoimmunotherapy (PIT) of cancer. Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed.
Parra, Jaime; Lopes da Silva, Fernando H; Stroink, Hans; Kalitzin, Stiliyan
Considering that the role of colour in photosensitive epilepsy (PSE) remains unclear, we designed a study to determine the potential of different colours, colour combinations and white light to trigger photoparoxysmal responses (PPRs) under stringent controlled conditions. After assessing their photosensitivity to stroboscopic white light and black and white patterns, we studied 43 consecutive PSE patients (mean age 19 years, 34 women), using a specially designed colour stimulator. Stimuli included: pulse trains between 10 and 30 Hz of white light and of all primary colours, and also isoluminant alternating time-sequences of colours. Illuminance was kept constant at 100 lux. A progressive stepwise increase of the modulation-depth (MD) of the stimuli was used to determine PPRs threshold. Whereas all the 43 patients were found to be sensitive during the stroboscopic and pattern protocol, only 25 showed PPRs (Waltz's score >2) at least in one session when studied with the colour stimulator. Coloured stimuli elicited PPRs in all these patients, whereas white light did so only in 17 patients. Of the primary colours, red elicited more PPRs (54 in 22 patients) and at a lower MD (max Z-score 0.93 at 10 Hz). Of the alternating sequences, the red-blue was the most provocative stimulus, especially below 30 Hz (100% of patients, max Z-score: 1.65 at 15 Hz). Blue-green was the least provocative stimulus, since it elicited only seven PPRs in seven (28%) patients (max Z-score 0.44 at 10 Hz). Sensitivity to alternating colours was not correlated to sensitivity to individual colours. We conclude that colour sensitivity follows two different mechanisms: one, dependent on colour modulation, plays a role at lower frequencies (<30 Hz). Another, dependent on single-colour light intensity modulation correlates to white light sensitivity and is activated at higher frequencies. Our results suggest that the prescription of spectacles with coloured lenses, tailored to the patient, can be an
Alfayez, Saud M.; Aljafen, Bandar N.
Objective: To assess the epilepsy services and identify the challenges in hospitals without epilepsy monitoring units (EMUs). In addition, comparisons between governmental and private sectors, as well as between regions, are to be performed. Methods: A cross-sectional study conducted using an online questionnaire distributed to the secondary and tertiary hospitals without EMUs throughout the Kingdom of Saudi Arabia (KSA). The study was conducted from September 2013 to September 2015 and regular updates from all respondents were constantly made. Items in the questionnaire included the region of the institution, the number of pediatric and adult neurologists and neurosurgeons along with their subspecialties, the number of beds in the Neurology Department, whether they provide educational services and have epilepsy clinics and if they refer patients to an EMU or intend to establish one in the future. Results: Forty-three institutions throughout the Kingdom responded, representing a response rate of 54%. The majority of hospitals (58.1%) had no adult epileptologists. A complete lack of pediatric epileptologists was observed in 72.1% of hospitals. Around 39.5% were utilizing beds from internal medicine. Hospitals with an epilepsy clinic represented 34.9% across all regions and sectors. Hospitals with no intention of establishing an EMU represented 53.5%. Hospitals that did not refer their epileptic patients to an EMU represented 30.2%. Conclusions: Epilepsy services in KSA hospitals without EMUs are underdeveloped. PMID:27744461
Gloss, David; Vickrey, Barbara
Marijuana appears to have anti-epileptic effects in animals. It is not currently known if it is effective in patients with epilepsy. Some states in the United States of America have explicitly approved its use for epilepsy. To assess the efficacy and safety of cannabinoids when used as monotherapy or add-on treatment for people with epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (9 September 2013), Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 8), MEDLINE (Ovid) (9 September 2013), ISI Web of Knowledge (9 September 2013), CINAHL (EBSCOhost) (9 September 2013), and ClinicalTrials.gov (9 September 2013). In addition, we included studies we personally knew about that were not found by the searches, as well as searched the references in the identified studies. Randomized controlled trials (RCTs) whether blinded or not. Two authors independently selected trials for inclusion and extracted the data. The primary outcome investigated was seizure freedom at one year or more, or three times the longest interseizure interval. Secondary outcomes included responder rate at six months or more, objective quality of life data, and adverse events. We found four randomized trial reports that included a total of 48 patients, each of which used cannabidiol as the treatment agent. One report was an abstract and another was a letter to the editor. Anti-epileptic drugs were continued in all studies. Details of randomisation were not included in any study report. There was no investigation of whether the control and treatment participant groups were the same or different. All the reports were low quality.The four reports only answered the secondary outcome about adverse effects. None of the patients in the treatment groups suffered adverse effects. No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy. The dose of 200 to 300 mg daily of cannabidiol was
Gloss, David; Vickrey, Barbara
Marijuana appears to have anti-epileptic effects in animals. It is not currently known if it is effective in patients with epilepsy. Some states in the United States of America have explicitly approved its use for epilepsy. To assess the efficacy of marijuana, or one of marijuana's constituents in the treatment of people with epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (May 15, 2012), the Cochrane Central Register of Controlled Trials (CENTRAL issue 4 of 12, The Cochrane Library 2012),MEDLINE (PubMed, searched on May 15, 2012), ISI Web of Knowledge (May 15, 2012), CINAHL (EBSCOhost, May 15, 2012), and ClinicalTrials.gov (May 15, 2012). In addition, we included studies we personally knew about that were not found by the searches, as well as references in the identified studies. Randomized controlled trials (RCTs), whether blinded or not. Two authors independently selected trials for inclusion and extracted data. The primary outcome investigated was seizure freedom at one year or more, or three times the longest interseizure interval. Secondary outcomes included: responder rate at six months or more, objective quality of life data, and adverse events. We found four randomized reports which included a total of 48 patients, each of which used cannabidiol as the treatment agent. One report was an abstract, and another was a letter to the editor. Anti-epileptic drugs were continued in all. Details of randomisation were not included in any study. There was no investigation of whether control and treatment groups were the same or different. All the reports were low quality.The four reports only answered the secondary outcome about adverse effects. None of the patients in the treatment groups suffered adverse effects. No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy. The dose of 200 to 300 mg daily of cannabidiol was safely administered to small numbers of patients, for generally
St Louis, Erik K; Cascino, Gregory D
This review identifies the diverse and variable clinical presentations associated with epilepsy that may create challenges in diagnosis and treatment. Epilepsy has recently been redefined as a disease characterized by one or more seizures with a relatively high recurrence risk (ie, 60% or greater likelihood). The implication of this definition for therapy is that antiepileptic drug therapy may be initiated following a first seizure in certain situations.EEG remains the most commonly used study in the evaluation of people with epilepsy. Routine EEG may assist in diagnosis, classification of seizure type(s), identification of treatment, and monitoring the efficacy of therapy. Video-EEG monitoring permits seizure classification, assessment of psychogenic nonepileptic seizures, and evaluation of candidacy for epilepsy surgery. MRI is pivotal in elucidating the etiology of the seizure disorder and in suggesting the localization of seizure onset. This article reviews the new International League Against Epilepsy practical clinical definition for epilepsy and the differential diagnosis of other physiologic paroxysmal spells, including syncope, parasomnias, transient ischemic attacks, and migraine, as well as psychogenic nonepileptic seizures. The initial investigational approaches to new-onset epilepsy are considered, including neuroimaging and neurophysiologic investigations with interictal and ictal video-EEG. Neurologists should maintain a high index of suspicion for epilepsy when children or adults present with a single paroxysmal spell or recurrent episodic events.
Höfler, Julia; Unterberger, Iris; Dobesberger, Judith; Kuchukhidze, Giorgi; Walser, Gerald; Trinka, Eugen
Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Tønnesen, Hanne Hjorth; Mysterud, Ivar; Karlsen, Jan; Skulberg, Olav M; Laane, Carl M M; Schumacher, Trond
Alveld is a hepatogenous photosensitivity disorder in lambs. Although alveld has been known in Norway for more than 100years, there are still questions related to the cause of the disease. Phytoporphyrin has long been incriminated as the photosensitizer in hepatogenous photosensitivity diseases but previous findings suggest that the photosensitizing mechanism in alveld is more complex, possibly involving other co-factors. The current work investigates the presence of non-hepatogenous photosensitizers originating in lamb's drinking water from various sources. In addition samples of two of the predominent cyanobacteria found in a representative biofilm (i.e. aggregates of microbes) were identified and isolated in axenic (i.e. pure) cultures. Information from the absorption-, fluorescence emission-, and -excitation spectra and the action spectrum for the formation of singlet oxygen was combined in order to identify the chromophores responsible for the formation of singlet oxygen, e.g. phycocyanins from the cyanobacteria. The highest level of singlet oxygen formation was detected in lotic (i.e. flowing) water in the period consistent with the outbreak of the alveld disease in the area. Meteorological data indicate a warm and wet May with a high radiation exposure leading up to a colder and wet June with an even higher solar irradiance. The seasonal variation in the amount of photosensitizers in lamb's drinking water combined meteorological data can be important to predict the outbreak of alveld. Copyright © 2012 Elsevier B.V. All rights reserved.
Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan
Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.
Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan
Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. No relevant studies were found. There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.
Wong, Judy; Wirrell, Elaine
To determine (a) whether children and teens with epilepsy participate in less physical activity and have higher body mass index (BMI) percentiles for age than do their siblings without epilepsy; and (b) what epilepsy-specific factors limit their participation. Patients 5-17 years, with a >or=3 month history of epilepsy, a development quotient >or=80, no major motor or sensory impairments, and at least one sibling without epilepsy in a similar age range, were identified from the Neurology Clinic database or at the time of clinic visit. Parents completed a questionnaire regarding sedentary activities and group, individual, and total sports activities. Children aged 11-15 years also completed the physical activity portion of the Health Behavior in School Aged Children questionnaire. Clinic charts were reviewed for seizure type, etiology, frequency, duration of epilepsy, and number of antiepileptic drugs (AEDs) ever taken. Teens with epilepsy participated in fewer group and total sports activities than did controls and were more likely to be potentially overweight or overweight. Receiving three or more AEDs in the past showed a significant negative correlation with sports participation. Although a trend was noted for those with higher seizure frequency to be less active, no other epilepsy-specific factors or prior seizures or seizure-related injury during a sports event correlated with participation in physical activity. Programs that promote exercise in adolescents with epilepsy should be encouraged to improve their physical, psychological, and social well-being.
Sinitsina, O O; Zholdakova, Z I; Poliakova, E E; Golovach, E N; Sycheva, L P; Beliaeva, N N; Kuznetsova, N A
The toxicity of the photosensitizers proflavine acetate (PA) versus methylene blue (MB) was evaluated during their varying destruction. Under the influence of visible light, a partial (25%) transformation of the photosensitizers was shown to be attended by their enhanced toxicity and 100% destruction of the parent substances caused a reduction in their hazard. PA and its phototransformation products mainly affect the antiperoxide protection system and the structural and functional states of the liver, kidney, and duodenum. The maximum noneffective dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends on the ratio of safe and effective concentrations. A partial (25%) MB destruction products cause mutagenic effects; the permissible dose of the mutagen is 0.00025 mg/kg. MB is not recommended for disinfection of all types of waters.
Anderson, David F.
In an ionization type detector for high energy radiation wherein the energy of incident radiation is absorbed through the ionization of a liquid noble gas and resulting free charge is collected to form a signal indicative of the energy of the incident radiation, an improvement comprising doping the liquid noble gas with photosensitive molecules to convert scintillation light due to recombination of ions, to additional free charge.
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Wagner, Janelle L; Smith, Gigi; Ferguson, Pamela L; Horton, Stephanie; Wilson, Erin
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.
BARCA, Diana; TARTA-ARSENE, Oana; DICA, Alice; ILIESCU, Catrinel; BUDISTEANU, Magdalena; MOTOESCU, Cristina; BUTOIANU, Niculina; CRAIU, Dana
Down Syndrome (DS) is the most common genetic cause of mental retardation, with a reported frequency of epilepsy between 1.4-17% (1). There is a paucity of data in the literature regarding epilepsy in Down syndrome and its relation to intellectual disability. Objectives: The purpose of this article is to analyze the association of epilepsy in children with DS - frequency and type of seizures, treatment, outcome and to compare cognitive impairment of children with DS and epilepsy and DS without epilepsy from our cohort. Methods: A four years systematic retrospective analysis of the database of the Pediatric Neurology Clinic (January 2010 - December 2013) identified a cohort of 39 pediatric cases with DS and neurological symptoms, 9 of them (23%) associating epileptic seizures. Following data were analysed: clinical and neurological examination, type/s of seizures, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), psychological examination, psychiatric evaluation in selected cases, electrocardiography (ECG), cardiac ultrasonography, ophthalmologic examination. Results: 23% (9 patients) of the children with DS of our cohort presented epilepsy. Five patients had epileptic spasms (56%), one of these further developed astatic seizures. Focal seizures were observed in three patients (33%) and absence with eyelid myoclonias in one patient (11%). Two of the nine patients with DS and epilepsy had generalized seizures, both with very good response to levetiracetam (LEV). EEG was abnormal at seizure onset, and was improved after treatment. Of the nine children with DS and epilepsy, two (22%) presented mild mental retardation and seven (78%) had moderate to severe cognitive delay. Of the 30 children with DS and without epilepsy, 21 (70%) had mild mental retardation and 9 (30%) had moderate to severe cognitive impairment. Conclusions: The most frequent epileptic syndrome associated with DS is West syndrome, with good response to specific antiepileptics
Fernandes, Paula T; Cabral, Paula; Araújo, Ulisses; Noronha, Ana Lúcia A; Li, Li M
Epilepsy remains a stigmatized condition. Lack of information has been pointed to as a cause of the perpetuation of stigma. Our goal was to survey children's perception of epilepsy. We used a questionnaire to determine if the children knew what epilepsy is and, if they did not know, what did they think epilepsy is. Twenty-nine children (15 girls; mean age 10 years, range 9-11 years) from a fourth-grade class of an elementary school in Campinas, Sao Paulo, Brazil, completed the questionnaires individually at the same time in the classroom. This took about 20 minutes. Only four children said they knew what epilepsy is: a disease of swallowing the tongue (3) and a disease that can kill (1). The perceptions of children who said they did not know what epilepsy is were: a disease that can kill, a disease of swallowing the tongue, a contagious disease, a serious illness, a head injury. Three children knew someone with epilepsy, and only two of them had said they knew what epilepsy is. The perceptions elicited from the children had a negative connotation; only one child mentioned a relationship between epilepsy and the brain. The spontaneous thoughts of children in this age group, without the contamination of political correctness, may reflect society's collective unconsciousness of the prejudice toward epilepsy and people with epilepsy and needs to be further investigated. Continuous, repetitive educational efforts are necessary in elementary school to change these negative perceptions of epilepsy in our society.
Rismanchi, Neggy; Gold, Jeffrey J; Sattar, Shifteh; Glaser, Carol A; Sheriff, Heather; Proudfoot, James; Mower, Andrew; Crawford, John R; Nespeca, Mark; Wang, Sonya G
To evaluate factors associated with the development of epilepsy after resolution of presumed childhood encephalitis. A total of 217 patients with suspected encephalitis who met criteria for the California Encephalitis Project were identified. Evaluable outcome information was available for 99 patients (40 girls, 59 boys, ages 2 months to 17 years) without preexisting neurological conditions, including prior seizures or abnormal brain magnetic resonance imaging scans. We identified factors correlated with the development of epilepsy after resolution of the acute illness. Development of epilepsy was correlated with the initial presenting sign of seizure (P < 0.001). With each additional antiepileptic drug used to control seizures, the odds ratio of developing epilepsy was increased twofold (P < 0.001). An abnormal electroencephalograph (P < 0.05) and longer hospital duration (median of 8 versus 21 days) also correlated with development of epilepsy (P < 0.01). The need for medically induced coma was associated with epilepsy (P < 0.001). Seizures in those patients were particularly refractory, often requiring longer than 24 hours to obtain seizure control. Individuals who required antiepileptic drugs at discharge (P < 0.001) or were readmitted after their acute illness (P < 0.001) were more likely to develop epilepsy. Of our patients who were able to wean antiepileptic drugs after being started during hospitalization, 42% were successfully tapered off within 6 months. Limited data are available on the risk of developing epilepsy after childhood encephalitis. This is the first study that not only identifies risk factors for the development of epilepsy, but also provides data regarding the success rate of discontinuing antiepileptic medication after resolution of encephalitis. Copyright © 2015 Elsevier Inc. All rights reserved.
Vu, Lily Chi; Piccenna, Loretta; Kwan, Patrick; O'Brien, Terence J
People who are 60 years old and older have the highest incidence of developing new-onset epilepsy. The increase of the ageing population has resulted in a greater number of patients with new-onset epilepsy or at risk of developing the condition. Previously published review articles regarding epilepsy in older patients have had a broad focus, including people who were diagnosed with epilepsy in childhood or in middle age. This review focuses on the causes, treatment, prognosis and psychosocial impact of new-onset epilepsy in people aged 60 years and over. Following a search of the medical electronic databases and relevant references, we identified 22 studies overall that met the inclusion criteria. Only four randomised clinical trials (RCTs) were identified comparing different antiepileptic drug treatments in this population, demonstrating that newer generation antiepileptic drugs, e.g. lamotrigine and levetiracetam, were generally better tolerated. One uncontrolled study provided promising evidence of good outcomes and safety for surgical resection as a treatment for people with uncontrolled seizures. Five studies reported that people 60 years and over with new-onset epilepsy have significant cognitive impairments, e.g. memory, and psychological issues including depression, anxiety and fatigue. We found that there is very limited evidence to guide treatment in people with Alzheimer's disease and epilepsy. The specific features of new-onset epilepsy in this target population significantly influences the choice of treatment. Cognitive and psychiatric screening before treatment may be useful for management. Two studies with proposed guidelines were identified, but no formal clinical practice guidelines exist for this special population to assist with appropriate management. There is a need for more RCTs that investigate effective treatments with limited side effects. More research studies on the psychosocial effects of new onset epilepsy, and long-term outcomes, for
Hesdorffer, Dale C; Trimble, Michael
Associations between epilepsy and musical or poetic composition have received little attention. We reviewed the literature on links between poetic and musical skills and epilepsy, limiting this to the Western canon. While several composers were said to have had epilepsy, John Hughes concluded that none of the major classical composers thought to have had epilepsy actually had it. The only composer with epilepsy that we could find was the contemporary composer, Hikari Oe, who has autism and developed epilepsy at age 15years. In his childhood years, his mother found that he had an ability to identify bird sound and keys of songs and began teaching him piano. Hikari is able to compose in his head when his seizures are not severe, but when his seizures worsen, his creativity is lost. Music critics have commented on the simplicity of his musical composition and its monotonous sound. Our failure to find evidence of musical composers with epilepsy finds parallels with poetry where there are virtually no established poets with epilepsy. Those with seizures include Lord George Byron in the setting of terminal illness, Algernon Swinburne who had alcohol-related seizures, Charles Lloyd who had seizures and psychosis, Edward Lear who had childhood onset seizures, and Vachel Lindsay. The possibility that Emily Dickinson had epilepsy is also discussed. It has not been possible to identify great talents with epilepsy who excel in poetic or musical composition. There are few published poets with epilepsy and no great composers. Why is this? Similarities between music and poetry include meter, tone, stress, rhythm, and form, and much poetry is sung with music. It is likely that great musical and poetic compositions demand a greater degree of concentration and memory than is possible in epilepsy, resulting in problems retaining a musical and mathematical structure over time. The lack of association between recognizable neuropsychiatric disorders and these skills is a gateway to
Geyer, James D; Geyer, Emery E; Fetterman, Zachary; Carney, Paul R
Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3.7% for women and 1.7% for men). Epilepsy is also a common neurological disorder with significant associated morbidity and impact on quality of life. We evaluated the severity and frequency of primary RLS in patients with localization-related temporal lobe epilepsy (TLE) and investigated the role of prodromal RLS symptoms as a warning sign and lateralizing indicator. All epilepsy patients seen in the outpatient clinic were screened for movement disorders from 2005 to 2015. Ninety-eight consecutive patients with localization-related TLE (50 right TLE and 48 left TLE) who met inclusion criteria were seen in the outpatient clinic. The control group consisted of 50 individuals with no history or immediate family history of epilepsy. Each patient was evaluated with the International Restless Legs Study Group (IRLSSG) questionnaire, NIH RLS diagnostic criteria, ferritin level, and comprehensive sleep screening including polysomnography. Furthermore, patients with obstructive sleep apnea or a definite cause of secondary restless legs syndrome such as low serum ferritin or serum iron levels were also excluded from the study. There was a significant association between the type of epilepsy and whether or not patients had RLS χ 2 (1)=10.17, p<.01, using the χ 2 Goodness of Fit Test. Based on the odds ratio, the odds of patients having RLS were 4.60 times higher if they had right temporal epilepsy than if they had left temporal epilepsy, serving as a potential lateralizing indicator. A prodromal sensation of worsening RLS occurred in some patients providing the opportunity to intervene at an earlier stage in this subgroup. We identified frequent moderate to severe RLS in patients with epilepsy. The frequency of RLS was much more common than would typically be seen in patients of similar
Social factors have been identified as key drivers of epilepsy care, outcomes, and disparities, but there is a limited understanding of what these factors are and how they translate into disparities. This targeted review provides an overview of the social determinants of health framework and applies this perspective to the literature about social and psychosocial factors in epilepsy; a social determinants of health--epilepsy model is proposed. The key social determinants of health in epilepsy include socioeconomic status, race/ethnicity, age, and gender. For example, low socioeconomic status and minority status have been associated with a higher risk of epilepsy, more hospitalizations and emergency room visits (versus neurology services), antiepileptic drug nonadherence, and a lower rate of epilepsy surgery. Such differences in care/treatment and outcomes translate into health disparities, many of which are considered unjust (inequitable) and modifiable through social action. Other social determinants of health include structural and sociocultural contextual conditions (e.g., health economy, policy, and social stigma/discrimination) and mediating mechanisms including material (e.g., housing), behavioral/biological (e.g., adherence), psychosocial (e.g., perceived stigma), and health system (e.g., access) factors. There are complex relationships among social determinants of health in epilepsy, which remain poorly understood and hamper efforts to address and eliminate disparities in epilepsy care and outcomes. Further empirical work grounded in sound theory and robust methodologies is needed to identify points of intervention and design effective and socially acceptable solutions to any pervasive disparities in epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.
Ablah, Elizabeth; Hesdorffer, Dale C; Liu, Yi; Paschal, Angelia M; Hawley, Suzanne; Thurman, David; Hauser, W Allen
To determine the prevalence of active epilepsy in two southeastern rural Kansas counties. Medical records were abstracted from the emergency rooms, out- and inpatient services and clinics of 9 hospitals, from 10 doctors' offices, and 1 nursing home in and surrounding the two counties. Letters were mailed from hospitals and doctors' offices to invite their potentially eligible patients to participate in an interview. Medical record information and the interview, when available, were used for the final determination of active epilepsy, seizure type, etiology, syndrome, age, and gender in consensus conferences. Prevalence of epilepsy was calculated, and capture-recapture methodology, which estimates prevalence based on what is known about the population, was employed to assess active epilepsy in the two counties. This study identified 404 individuals with active prevalent epilepsy who visited at least one of the 20 facilities during the observation period. The overall prevalence of active epilepsy was 7.2 per 1000. The seizure type for 71.3% of prevalent cases was unknown; among the 76 cases with known and classifiable seizure type, 55.3% had focal with secondary generalized seizures. Among the 222 cases with classifiable etiology, 53.1% were idiopathic/cryptogenic. About 75% (n=301) were captured at only one center, 72% (n=75) of the remaining 103 patients were captured at two centers, and 28 patients were identified at three or more centers. The capture-recapture assessment yielded an estimation of 982 prevalent patients. The overall estimated prevalence of epilepsy in the two Kansas counties using capture-recapture was 17 per 1000. The crude prevalence of epilepsy, using medical record survey methods, was similar to, but on the high end, of other total population prevalence studies in the United States. The capture-recapture assessment suggested that epilepsy prevalence might be considerably higher than the crude prevalence. Copyright © 2014 Elsevier B.V. All
Ramaratnam, S; Sridharan, K
Stress is considered an important precipitating factor for seizures. Yoga is believed to induce relaxation and stress reduction. The effect of yoga on the EEG and the autonomic nervous system have been reported. Yoga would be an attractive therapeutic option for epilepsy (if proved effective), in view of its nonpharmacological nature, minimal side effects and international acceptance. To assess the efficacy of yoga in the treatment of patients with epilepsy. We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (The Cochrane Library Issue 4, 1998), MEDLINE for articles published up to the middle of 1998, and also registries of the research council for complimentary medicine were searched. In addition, we searched the references of all the identified studies. Finally, we contacted the members of the Neurological Society of India, several neurophysiology institutions and yoga institutes to seek any ongoing studies or studies published in nonindexed journals or unpublished studies. Randomized control trials and controlled clinical trials of treatment of epilepsy with yoga. The data were extracted independently by both reviewers and any discrepancies were resolved by discussion. The main outcomes assessed were percentage of patients rendered seizure free, number of patients with more than 50% reduction in seizure frequency or seizure duration and the overall reduction in seizure frequency. Analyses were on an intention to treat basis. Only one study met the selection criteria, and recruited a total of 32 patients, 10 to sahaja yoga and 22 to control treatments. Antiepileptic drugs were continued in all. Randomization was by roll of a dice. The results of this study are as follows: (i) Four patients treated with yoga were seizure free for six months compared to none in the control groups. The Odds Ratio (OR) (95% Confidence Interval (CI)) for yoga versus sham yoga group was 14.5 (0.7, 316.7) and for yoga versus no treatment
Yrondi, A; Arbus, C; Valton, L; Schmitt, L
Historically, there is a strong link between depression and epilepsy. Patients with epilepsy are four to five times more likely to develop a depressive syndrome. It seems that the link between epilepsy and depression is bidirectional. There is little data on mood disorders secondary to epilepsy surgery. The goal of epilepsy surgery is to reduce the number and frequency of attacks, which in turn would allow improvements in mood disorders and cognitive impairment. A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The following MESH terms were used: epilepsy surgery AND (depression OR depressive disorder OR mood disorder). We also used the "related articles" of PubMed, bibliography surveys, conference abstracts and Google Scholar to identify additional relevant papers. Of the 130 studies found by the systematic search, 112 are excluded because they did not take into account the mood disorders secondary to epilepsy surgery. Fifteen studies are included in this review of the literature with a case study. Depression is the psychopathological condition that is the most frequently studied. According to several studies, the prevalence of depression is approximately 30% with nearly 70% of cases diagnosed during the first three months following epilepsy surgery. The majority of patients presented depressive symptoms during the first 3 to 12months after epilepsy surgery. In these studies, the risk of developing depression is correlated with the existence of previous depressive elements relative to the epilepsy surgery. A small number of studies reported cases of de novo depression. Studies have shown a correlation between very good to excellent control of epileptic seizures and a persistent improvement of mood disorders. It would seem that depressive symptoms post-surgery are more common when the surgical intervention concerns the temporal lobe and in particular mesial resections. There are only very
Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin
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.
A Novel RNA Editing Sensor Tool and a Specific Agonist Determine Neuronal Protein Expression of RNA-Edited Glycine Receptors and Identify a Genomic APOBEC1 Dimorphism as a New Genetic Risk Factor of Epilepsy
Kankowski, Svenja; Förstera, Benjamin; Winkelmann, Aline; Knauff, Pina; Wanker, Erich E.; You, Xintian A.; Semtner, Marcus; Hetsch, Florian; Meier, Jochen C.
C-to-U RNA editing of glycine receptors (GlyR) can play an important role in disease progression of temporal lobe epilepsy (TLE) as it may contribute in a neuron type-specific way to neuropsychiatric symptoms of the disease. It is therefore necessary to develop tools that allow identification of neuron types that express RNA-edited GlyR protein. In this study, we identify NH4 as agonist of C-to-U RNA edited GlyRs. Furthermore, we generated a new molecular C-to-U RNA editing sensor tool that detects Apobec-1- dependent RNA editing in HEPG2 cells and rat primary hippocampal neurons. Using this sensor combined with NH4 application, we were able to identify C-to-U RNA editing-competent neurons and expression of C-to-U RNA-edited GlyR protein in neurons. Bioinformatic analysis of 1,000 Genome Project Phase 3 allele frequencies coding for human Apobec-1 80M and 80I variants showed differences between populations, and the results revealed a preference of the 80I variant to generate RNA-edited GlyR protein. Finally, we established a new PCR-based restriction fragment length polymorphism (RFLP) approach to profile mRNA expression with regard to the genetic APOBEC1 dimorphism of patients with intractable temporal lobe epilepsy (iTLE) and found that the patients fall into two groups. Patients with expression of the Apobec-1 80I variant mostly suffered from simple or complex partial seizures, whereas patients with 80M expression exhibited secondarily generalized seizure activity. Thus, our method allows the characterization of Apobec-1 80M and 80l variants in the brain and provides a new way to epidemiologically and semiologically classify iTLE according to the two different APOBEC1 alleles. Together, these results demonstrate Apobec-1-dependent expression of RNA-edited GlyR protein in neurons and identify the APOBEC1 80I/M-coding alleles as new genetic risk factors for iTLE patients. PMID:29375302
Rand, Barry [Princeton, NJ; Forrest, Stephen R [Ann Arbor, MI; Mutolo, Kristin L [Hollywood, CA; Mayo, Elizabeth [Alhambra, CA; Thompson, Mark E [Anaheim Hills, CA
An organic photosensitive optoelectronic device, having a donor-acceptor heterojunction of a donor-like material and an acceptor-like material and methods of making such devices is provided. At least one of the donor-like material and the acceptor-like material includes a subphthalocyanine, a subporphyrin, and/or a subporphyrazine compound; and/or the device optionally has at least one of a blocking layer or a charge transport layer, where the blocking layer and/or the charge transport layer includes a subphthalocyanine, a subporphyrin, and/or a subporphyrazine compound.
Bianco, Andrea; Colella, Letizia; Galli, Paola; Zanutta, Alessio; Bertarelli, Chiara
Volume phase holographic elements are becoming attractive thanks to the large efficiency and good optical quality. They are based on photosensitive materials where a modulation of the refractive index is induced. In this paper, we highlight the strategies to obtain a change in the refractive index in a dielectric material, namely a change in the material density and/or in the molecular polarizability. Moreover, we show the results achieved for materials that undergo the photo-Fries reaction as function of the molecular structure and the illumination conditions. We also report the results on a system based on the diazo Meldrum's acid where volatile molecules are produced upon light exposure.
Shah, Ritesh; Botre, Abhijit; Udani, Vrajesh
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.
Mallikaratchy, Prabodhika; Tang, Zhiwen
This paper describes the application of a molecular construct of a photosensitizer and an aptamer for photo-therapeutically targeting tumor cells. The key step in increasing selectivity in chemotherapeutic drugs is to create effective molecular platforms that could target cancer cells but not normal cells. Recently, we have developed a strategy via cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to obtain cell specific aptamers using intact viable cells as targets to select aptamers that can recognize cell membrane proteins with high selectivity and excellent affinity. We have identified an aptamer TD05 that only recognizes Ramos cells, a Burkitt’s lymphoma cell line. Here, the high specificity of aptamers in target cell binding and an efficient phototherapy reagent, Ce6, are molecularly engineered to construct a highly selective Aptamer-photosensitizer conjugates (APS) to effectively destroy target cancer cells. Introduction of the APS conjugates followed by irradiation of light selectively destroyed target Ramos cells but not acute lymphoblastic leukemia and myeloid leukemia cell lines. This study demonstrates that the use of cancer specific aptamers conjugated to a photosensitizer will enhance the selectivity of photodynamic therapy. Coupled with the advantages of the cell-SELEX in generating multiple effective aptamers for diseased cell recognition, we will be able to develop highly efficient photosensitizer based therapeutical reagents for clinical applications. PMID:18058891
Johnson, Emily L; Kaplan, Peter W
Approximately 25 million individuals older than age 15 identify as transgender, representing about 0.3-0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy. We performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures. There are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated. Transgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender-affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
McKee, Jerry R.; Bodfish, James W.
Medical records of residents of a facility for persons with mental retardation from January 1, 1978, through December 31, 1997, were analyzed to identify incidence of sudden unexpected death for 180 individuals with and 125 without comorbid epilepsy. Eighty deaths were identified, with 55 occurring in those with epilepsy. (Contains 15 references.)…
Błaszczyk, Barbara; Czuczwar, Stanisław J
Depression episodes in epilepsy is the most common commorbidity, affecting between 11% and 62% of patients with epilepsy. Although researchers have documented a strong association between epilepsy and psychiatric comorbidities, the nature of this relationship is poorly understood. The manifestation of depression in epilepsy is a complex issue having many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Other risk factors are a family history of psychiatric illness, particularly depression, a lack of control over the seizures and iatrogenic causes (pharmacologic and surgical). In addition, treatment with antiepileptic drugs (AEDs) as well as social coping and adaptation skills have also been recognised as risk factors of depression associated with epilepsy. Epilepsy may foster the development of depression through being exposed to chronic stress. The uncertainty and unpredictability of seizures may instigate sadness, loneliness, despair, low self-esteem, and self-reproach in patients with epilepsy and lead to social isolation, stigmatization, or disability. Often, depression is viewed as a reaction to epilepsy's stigma and the associated poor quality of life. Moreover, patients with epilepsy display a 4-5 higher rate of depression and suicide compared with healthy population. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.
Epilepsy is one of the most common neurological disorders. Global neurological knowledge is essential for differential diagnosis of epileptic syndromes due to the diversity of ictal semiology, causes and syndromes. Neurologists play an important role in planning the medical care for patients with epilepsy, as medication is the most fundamental therapeutic strategy. Some patients with early-onset epilepsy require joint care by pediatric neurologists, those with intractable epilepsy by neurosurgeons, and those with psychological comorbidity by psychiatrists, and neurologists should play a coordinating role. While there is a great need for neurologists to participate in epilepsy care, neurologists in Japan currently do not participate substantially in the epilepsy management system. It is necessary to train more neurologists who can provide epilepsy care and conduct basic and clinical research on epilepsy by providing continuous education on epilepsy for general neurologists as well as pre- and post-graduate medical students. Most of the patients who require long-term treatment experience many medical problems and social handicaps, such as adverse effects of medication, social stigma, educational disadvantages and difficulties in obtaining driver's license. To improve the quality of life of patients with epilepsy, it is desirable to build broad medical-social networks participated by patients, doctors, neurological nurses, psychologists, social workers, school teachers, managers of employment support facilities and care givers.
... brain. Devices to treat epilepsy include vagus nerve stimulation and responsive neurostimulation. Who Treats Epilepsy? A general ... Many men with epilepsy will experience changes in sexual drive and performance. For example, many men report ...
Park, Wooram; Park, Sin-Jung; Cho, Soojeong
A switchable photosensitizer (PS), which can be activated at a spe-cific condition beside light, has tremendous advantages for photo-dynamic therapy (PDT). Herein, we developed a thermo-switchable polymeric photosensitizer (T-PPS) by conjugating PS (Pheophor-bide-a, PPb-a) to a temperature-responsive polymer backbone of biocompatible hydroxypropyl cellulose (HPC). Self-quenched PS molecules linked in close proximity by pi-pi stacking in T-PPS were easily transited to an active monomeric state by the tempera-ture induced phase transition of polymer backbones. The tempera-ture responsive inter-molecular interaction changes of PS molecules in T-PPS were demonstrated in synchrotron small-angle X-ray scattering (SAXS) and UV-Vis spectrophotometer analysis. The T-PPS allowed switchablemore » activation and synergistically enhanced cancer cell killing effect at the hyperthermia temperature (45 °C). Our developed T-PPS has the considerable potential not only as a new class of photomedicine in clinics but also as a biosensor based on temperature responsiveness.« less
Chen, Chia-Ying; Zepp, Richard G
Carbon nanotubes (CNTs) photosensitize the production of reactive oxygen species that may damage organisms by biomembrane oxidation or mediate environmental transformations of CNTs. Photosensitization by derivatized carbon nanotubes from various synthetic methods, and thus with different intrinsic characteristics (e.g., diameter and electronic properties), has been investigated under environmentally relevant aquatic conditions. We used the CNT-sensitized photoisomerization of sorbic acid ((2E,4E)-hexa-2,4-dienoic acid) and singlet oxygen formation to quantify the triplet states ((3)CNT*) formed upon irradiation of selected single-walled carbon nanotubes (SWCNTs) and multiwalled carbon nanotubes (MWCNTs). The CNTs used in our studies were derivatized by carboxyl groups to facilitate their dispersion in water. Results indicate that high-defect-density (thus well-stabilized), small-diameter, and semiconducting-rich CNTs have higher-measured excited triplet state formation and therefore singlet oxygen ((1)O2) yield. Derivatized SWCNTs were significantly more photoreactive than derivatized MWCNTs. Moreover, addition of sodium chloride resulted in increased aggregation and small increases in (1)O2 production of CNTs. The most photoreactive CNTs exhibited comparable photoreactivity (in terms of (3)CNT* formation and (1)O2 yield) to reference natural organic matter (NOM) under sunlight irradiation with the same mass-based concentration. Selected reference NOM could therefore be useful in evaluating environmental photoreactivity or intended antibacterial applications of CNTs.
Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; López-Escobar, M.; Arce-Diego, J. L.
Photodynamic Therapy involves the therapeutic use of photosensitizers in combination with visible light. The subsequent photochemical reactions generate reactive oxygen species which are considered the principal cytotoxic agents to induce cell death. This technique has become widely used in medicine to treat tumors and other nonmalignant diseases. However, there are several factors related to illumination or the photosensitizer that limit an optimal treatment outcome. The use of nanoparticles (NP) for PDT has been proposed as a solution to current shortcomings. In this way, there are NPs that act as carriers for photosensitizers, NPs that absorb the light and transfer the energy to the photosensitizer and NPs that are themselves photodynamically active. In dermatology, the use of topical photosensitizers produces a time dependent inhomogeneous distribution within the tumor, where the stratum corneum is the main barrier to the diffusion of the photosensitizer to the deeper layers of skin. This produces an insufficient photosensitizer accumulation in tumor tissues and therefore, a low therapeutic efficiency in the case of deep lesions. This work focuses in the use of NPs as photosensitizer carriers to improve the actual topical drug distribution in malignant skin tissues. We present a mathematical model of PS distribution in tumor tissue using NPs that takes into account parameters related to nanoparticles binding. Once the concentration profile of NPs into tissue is obtained, we use a photochemical model which allows us to calculate the temporal evolution of reactive oxygen species according to PS distribution calculated previously from NPs profile.
Loring, David W; Larrabee, Glenn J; Meador, Kimford J; Lee, Gregory P
We performed principal component analysis (PCA) of the Epilepsy Foundation Concerns Index scale in 189 patients undergoing evaluation for epilepsy surgery. We identified a five-factor solution in which there were no varimax-rotated factors consisting of fewer than two questions. Factor 1 reflects affective impact on enjoyment of life, Factor 2 reflects general autonomy concerns, Factor 3 reflects fear of seizure recurrence, Factor 4 reflects concern of being a burden to one's family, and Factor 5 reflects a perceived lack of understanding by others. Multiple regression using the Quality of Life in Epilepsy--89 question version; Minnesota Multiphasic Personality Inventory--2; Wechsler Adult Intelligence Scale--third edition; and verbal and visual memory tests as predictors demonstrated a different pattern of association with the factor and summary scores. We conclude that the Epilepsy Foundation Concerns Index is multidimensional, and using a global score based on all items may mask specific concerns that may be relevant when applied to individual patients.
Striano, Pasquale; Zara, Federico
The term 'cortical tremor' was first introduced by Ikeda and colleagues to indicate a postural and action-induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug-resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well-delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.
Ferlisi, Monica; Shorvon, Simon
adult epilepsy clinic population: (a) to identify the frequency of seizure precipitants (triggering factors) and their relative frequency in those with psychiatric disorders, and in those in remission or with active epilepsy, differences in frequency with regard to gender, seizure duration, number of drugs taken; (b) to determine which precipitants patients most commonly report; and (c) to identify differences in the distribution of precipitants among generalized, temporal, and extratemporal epilepsies. Consecutive patients attending a tertiary-care epilepsy clinic were prospectively and an open personal interview to identify and characterize seizure precipitants. Information about the epilepsy and clinical characteristics of patients was collected during the interview and from medical records. Of 104 patients, 97% cited at least one precipitant. Stress, sleep deprivation, and fatigue were the most frequently reported precipitants. Patients with psychological comorbidities reported a greater percentage of seizures with seizure precipitants. Patients with idiopathic generalized epilepsy seemed to be more sensitive to seizures during awakening and sleep deprivation, patients with extratemporal epilepsy reported more frequent seizures during sleep. There were no differences in frequency or type of seizure precipitants with regard to gender, seizure duration or frequency, and the number of antiepileptic drugs taken. The findings may have implications for the better management of epilepsy by increasing a focus on nonpharmacological therapy. The implications of the findings for nosology and causation of epilepsy are also briefly discussed. Copyright © 2014 Elsevier Inc. All rights reserved.
Md, Shadab; Haque, Shadabul; Madheswaran, Thiagarajan; Zeeshan, Farrukh; Meka, Venkata Srikanth; Radhakrishnan, Ammu K; Kesharwani, Prashant
Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT. Copyright © 2017 Elsevier Ltd. All rights reserved.
Owczarek, K; Jędrzejczak, J
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.
Harroud, Adil; Bouthillier, Alain; Weil, Alexander G.; Nguyen, Dang Khoa
Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE. PMID:22934162
Olson, Heather; Shen, Yiping; Avallone, Jennifer; Sheidley, Beth R.; Pinsky, Rebecca; Bergin, Ann M.; Berry, Gerard T.; Duffy, Frank H.; Eksioglu, Yaman; Harris, David J.; Hisama, Fuki M.; Ho, Eugenia; Irons, Mira; Jacobsen, Christina M.; James, Philip; Kothare, Sanjeev; Khwaja, Omar; Lipton, Jonathan; Loddenkemper, Tobias; Markowitz, Jennifer; Maski, Kiran; Megerian, J. Thomas; Neilan, Edward; Raffalli, Peter C.; Robbins, Michael; Roberts, Amy; Roe, Eugene; Rollins, Caitlin; Sahin, Mustafa; Sarco, Dean; Schonwald, Alison; Smith, Sharon E.; Soul, Janet; Stoler, Joan M.; Takeoka, Masanori; Tan, Wen-Han; Torres, Alcy R.; Tsai, Peter; Urion, David K.; Weissman, Laura; Wolff, Robert; Wu, Bai-Lin; Miller, David T.; Poduri, Annapurna
Objective To evaluate the role of copy number abnormalities detectable by chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center. Methods We identified patients with ICD-9 codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children’s Hospital. We reviewed medical records and included patients meeting criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA. Results Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1–4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18 kb to 142 Mb, and 34% were over 500 kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots.” We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy. Interpretation Copy number abnormalities play an important role in patients with epilepsy. Given that the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy. PMID:24811917
Speed, Doug; O'Brien, Terence J; Palotie, Aarno; Shkura, Kirill; Marson, Anthony G; Balding, David J; Johnson, Michael R
Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.
Niedzielska, Krystyna; Wolańczyk, Tomasz; Baker, Gus A; Jakoby, Ann; Doughty, Julie; De Boer, Hanneke
The main aim of the European Study SPOKE (Sanofi-Synthelabo Programme for Outcome Knowledge of Epilepsy) designed by the Department of Neurosciences, Walton Hospital in Liverpool and the Centre for Health Services Research at the University of Newcastle upon Tyne, England, was to describe levels of knowledge about epilepsy among people with epilepsy and their families. It was equally important to identify gaps in understanding the most important aspects of the illness as well as to identify characteristics of people who score poorly on the Epilepsy Knowledge Questionnaire (EKQ). Another aim was to consider the implications of identified gaps in knowledge for future educational and psychosocial interventions. The study was conducted in 10 European countries and included 6156 people with epilepsy and 6506 members of their families. Results presented here relate to data for Poland only, where the examined population consisted of 1028 patients with epilepsy. 1033 questionnaires were returned by carers. Over 40% of all respondents had frequent seizures, and one third were seizure free. Scores on the Epilepsy Knowledge Questionnaire were high for the majority of respondents, but generally lower than in most of the countries. With reference to some aspects of illness important gaps in knowledge have been demonstrated. For example, it was shown that a significant number of respondents provided incorrect answers to questions relating to aspects of the etiology of epilepsy and administration of antiepileptic drug medication. There were a number of significant differences between the profiles of high and low scorers on the EKQ; high scorers were likely to have spent longer on education, have lower scores on the impact of epilepsy scale and report better adjustment to their epilepsy. The results of the study once again underline the importance of continued information among patients with epilepsy and their families in order to achieve.
Lee, Sang-Ahm; Yim, Soo Bin; Rho, Young Il; Chu, Minkyung; Park, Hyeon Mi; Lee, Geun-ho; Park, Sung-Pa; Jung, Dae Soo
We investigated factors contributing to teachers' attitudes toward students with epilepsy. Data were collected from 604 teachers in Korea. The questionnaire included the Scale of Attitudes Toward Persons with Epilepsy (ATPE) and a demographic and teaching experience survey. In stepwise linear regression analysis, ATPE Knowledge scores (P<0.001) and prior experience teaching a student with epilepsy (P=0.001) were identified as significant factors for ATPE Attitude scores. The ATPE Knowledge scores accounted for 50.1% of the variance in the Attitude scores, and experience teaching a student with epilepsy accounted only for 1.0%. Our finding that teachers' knowledge is the most important factor influencing teacher's attitudes toward epilepsy indicates that teachers should be provided with information about epilepsy universally, across geographic settings, educational levels, and experience levels. Copyright © 2010 Elsevier Inc. All rights reserved.
Kim, Myeong-Kyu; Kwon, Oh-Young; Cho, Yong-Won; Kim, Yosik; Kim, Sung-Eun; Kim, Hoo-Won; Lee, Sang Kun; Jung, Ki-Young; Lee, Il Keun
A multicentre face-to-face interview was conducted to identify factors contributing to the marital status of people with epilepsy (PWE) in Korea. The marriage rate of PWEs was only 80% and the divorce rate was more than double that in the general population. Among the single subjects, 34% replied that they were unmarried because of epilepsy, and 76% of divorced PWEs replied that epilepsy was the cause of the divorce. The factors affecting the single and divorced status in PWEs included gender, an earlier onset of seizure and seizure onset before marriage. Not informing the spouse of the disease before marriage for fear of discrimination was not related to disadvantage in marriage negotiation or to divorce. Social stigmatization of epilepsy continues and impacts on the marital status of PWEs in Korea. However, there is no correlation between the perceived and the enacted stigmas of epilepsy. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Mlinar, Simona; Petek, Davorina; Cotič, Živa; Mencin Čeplak, Metka; Zaletel, Marjan
Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE's social network, which leads to (self-)isolation and social distrust. PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy.
Shankar, Rohit; Rowe, Charles; Van Hoorn, Alje; Henley, William; Laugharne, Richard; Cox, David; Pande, Raj; Roy, Ashok; Sander, Josemir W
One quarter of people with epilepsy have an intellectual disability (ID) and one fifth of people with an ID have epilepsy. Both conditions are associated with higher levels of morbidity, stigma and premature mortality. There have been calls for action to promote more research in this group. We examined if this group are represented adequately in current research. The proportion of research output in epilepsy conferences and publications relevant to ID and the proportion in ID conferences and publications on epilepsy for 2015-2016 were identified. As the percentage of children in the population with epilepsy is 17%, research output of this group was compared with the ID group. Recognised material was classified based on whether it applied to general epilepsy/ID research, children with epilepsy or people with epilepsy and ID. Data was analysed to determine the proportion of presented research specifically identifying people with epilepsy and ID. Fewer than 2% of presentations at epilepsy conferences specifically related to the ID and epilepsy group compared to 15% relating to children with epilepsy. Similarly only 1.4% of the research presented at major ID conferences related to those with people with epilepsy and ID. About 5% of published research in the field of epilepsy related to those with ID as compared with 24% for children with epilepsy. Twelve percent of published research in ID specifically identified epilepsy. Publications and conference presentations, on the population with epilepsy and comorbid ID is under-represented. Increased research in this area might assist in improving the quality of care for this relatively neglected group.
Kellinghaus, Christoph; Lüders, Hans O
Frontal lobe epilepsy accounts for only 10-20% of the patients in surgical series, but the incidence in non-surgical patient cohorts seems to be much higher. The typical clinical presentation of the seizures includes contralateral clonic movements, uni- or bilateral tonic motor activity as well as complex automatism. The yield of surface EEG may be limited due to the difficulty in detection of mesial or basal foci, and the patient may be misdiagnosed as having non-epileptic events. In addition, in patients with mesial frontal foci the epileptiform discharges may be mislateralized ("paradoxical lateralization"). Therefore, epilepsy surgery has been commonly considered as less promising in patients with frontal lobe epilepsy. However, the advent of sophisticated neuroimaging techniques, particularly MRI with epilepsy-specific sequences, has made it possible to delineate the epileptogenic lesion and detect a specific etiology, in an increasing number of patients. Thus, the success rate of epilepsy surgery in frontal lobe epilepsy is currently comparable to temporal lobe epilepsy, if the candidates are carefully selected. Patients with frontal lobe epilepsy who do not respond to anticonvulsive medication, and who are not eligible for epilepsy surgery may benefit from alternative approaches such as electrical brain stimulation.
Bandstra, Nancy F; Camfield, Carol S; Camfield, Peter R
Epilepsy directly affects 50 million people worldwide. Most can achieve excellent seizure control; however, people living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions and misunderstandings that have persisted for thousands of years. This paper reviews the frequency and nature of stigma toward epilepsy. Significant negative attitudes prevail in the adolescent and adult public worldwide leading to loneliness and social avoidance both in school and in the workplace. People with epilepsy are often wrongly viewed as having mental health and antisocial issues and as being potentially violent toward others. Twenty-five percent of adults having epilepsy describe social stigma as a result of their epilepsy. They fear rejection and often feel shame or loneliness from this diagnosis. The psychosocial and social impact of epilepsy is significant. Yet few specific interventions have been demonstrated to alter this perception. The effect on public education is primarily short-term, while change over the long-term in attitudes and inaccurate beliefs have not presently been proven effective. School education programming demonstrates improved knowledge and attitude a month after a classroom intervention, but persisting change over a longer period of time has not been evaluated. In-depth adult psycho-educational programs for adults with epilepsy improves knowledge, coping skills and level of felt stigma. However these gains have not demonstrated persistence over time. Myths, misconceptions and misunderstandings about epilepsy continue and programs aimed at increasing knowledge and reducing negative public attitudes should be enhanced.
Kotova, O V; Akarachkova, E S
The review of the literature on sleep disorders in epilepsy over the last two decades is presented. Paroxysmal phenomena of epileptic origin, nonepileptic paroxysms, antiepileptic drugs, polypragmasia and comorbid depression may affect sleep in epilepsy.Shortening of sleep time may cause seizures, hallucinations and depression because sleep plays an important role in the regulation of excitatory and inhibitory processes in the brain both in healthy people and in patients with epilepsy. According to the literature data, drugs (short treatment courses of hypnotics) or nonpharmacological methods should be used for treatment insomnia inpatients with epilepsy.
Wagner, Ryan G; Newton, Charles R
Both helminthiases and epilepsy occur globally, and are particularly prevalent in developing regions of the world. Studies have suggested an association between epilepsy and helminth infection, but a causal relationship is not established in many helminths, except perhaps with neurocysticercosis. We review the available literature on the global burden of helminths, and the epidemiological evidence linking helminths to epilepsy. We discuss possible routes that helminths affect the central nervous system of humans and the immunological response to helminth infection in the central nervous system, looking at possible mechanisms of epileptogenesis. Finally, we discuss the current gaps in knowledge about the interaction between helminths and epilepsy. PMID:19825109
Strzelczyk, Adam; Reese, Jens Peter; Dodel, Richard; Hamer, Hajo M
The objective of this review was to overview published cost-of-illness (COI) studies of epilepsy and their methodological approaches. Epilepsy imposes a substantial burden on individuals and society as a whole. The mean prevalence of epilepsy is estimated at 0.52% in Europe, 0.68% in the US, and peaks up to 1.5% in developing countries. Estimation of the economic burden of epilepsy is of pivotal relevance to enable a rational distribution of healthcare resources. This is especially so with the introduction of the newer antiepileptic drugs (AEDs), the marketing of vagal-nerve stimulators and the resurgence of new surgical treatment options, which have the potential to considerably increase the costs of treating epilepsy.A systematic literature review was performed to identify studies that evaluated direct and indirect costs of epilepsy. Using a standardized assessment form, information on the study design, methodological framework and data sources were extracted from each publication and systematically reported. We identified 22 studies worldwide on costs of epilepsy. The majority of the studies reflected the costs of epilepsy in Europe (three studies each for the UK and Italy, one study each for Germany, the Netherlands, Switzerland, France and the EU) and the US (four studies), but studies were also available from India (two), Hong Kong, Oman, Burundi, Chile and Mexico. The studies utilized different frameworks to evaluate costs. All used a bottom-up approach; however, only 12 studies (55%) evaluated direct as well as indirect costs. The range for the mean annual direct costs lay between 40 International Dollar purchasing power parities (PPP-$) in rural Burundi and PPP-$4748 (adjusted to 2006 values) in a German epilepsy centre. Recent studies suggest AEDs are becoming the main contributor to direct costs. The mean indirect costs ranged between 12% and 85% of the total annual costs. Epilepsy is a cost-intensive disorder. A reliable comparison of the different COI
Lamberts, Robert J.; Blom, Marieke T.; Wassenaar, Merel; Bardai, Abdennasser; Leijten, Frans S.; de Haan, Gerrit-Jan; Sander, Josemir W.; Thijs, Roland D.
Objective: To ascertain whether characteristics of ventricular tachycardia/fibrillation (VT/VF) differed between people with epilepsy and those without and which individuals with epilepsy were at highest risk. Methods: We ascertained 18 people with active epilepsy identified in a community-based registry of sudden cardiac arrest (SCA) with ECG-confirmed VT/VF (cases). We compared them with 470 individuals with VT/VF without epilepsy (VT/VF controls) and 54 individuals with epilepsy without VT/VF (epilepsy controls). Data on comorbidity, epilepsy severity, and medication use were collected and entered into (conditional) logistic regression models to identify determinants of VT/VF in epilepsy. Results: In most cases, there was an obvious (10/18) or presumed cardiovascular cause (5/18) in view of preexisting heart disease. In 2 of the 3 remaining events, near–sudden unexpected death in epilepsy (SUDEP) was established after successful resuscitation. Cases had a higher prevalence of congenital/inherited heart disease (17% vs 1%, p = 0.002), and experienced VT/VF at younger age (57 vs 64 years, p = 0.023) than VT/VF controls. VT/VF in cases occurred more frequently at/near home (89% vs 58%, p = 0.009), and was less frequently witnessed (72% vs 89%, p = 0.048) than in VT/VF controls. Cases more frequently had clinically relevant heart disease (50% vs 15%, p = 0.005) and intellectual disability (28% vs 1%, p < 0.001) than epilepsy controls. Conclusion: Cardiovascular disease rather than epilepsy characteristics is the main determinant of VT/VF in people with epilepsy in the community. SCA and SUDEP are partially overlapping disease entities. PMID:26092917
Cuccaro, Michael L.; Tuchman, Roberto F.; Hamilton, Kara L.; Wright, Harry H.; Abramson, Ruth K.; Haines, Jonathan L.; Gilbert, John R.; Pericak-Vance, Margaret
Epilepsy co-occurs frequently in autism spectrum disorders (ASD). Understanding this co-occurrence requires a better understanding of the ASD-epilepsy phenotype (or phenotypes). To address this, we conducted latent class cluster analysis (LCCA) on an ASD dataset (N = 577) which included 64 individuals with epilepsy. We identified a 5-cluster…
Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.
Araújo, Patrícia V; Teixeira, Karina I R; Lanza, Lincoln D; Cortes, Maria E; Poletto, Luiz T A
The purpose of this in vitro study was to evaluate the antimicrobial effect of photodynamic therapy on Streptococcus mutans (A TCC 25175) suspensions, using a red laser for one minute in combination with toluidine blue O (TBO) or methylene blue (MB). Both photosensitizers were used in three concentrations (25, 10 and 5 mg/L). The activity ofphotosensitizers and laser irradiation were tested separately on the bacteria, as well as the irradiation of this light source in the presence of the TBO or MB. These groups were compared to a control group, in which the microorganism did not receive any treatment. The activity of both TBO and MB or laser irradiation, alone, were not able to reduce the number of S. mutans. In the groups of lethal photosensitization, a bacterial reduction of 70% for TBO and 73% for MB was observed when these photosensitizers were used at 25 mg/L and a reduction of 48% was observed for MB at 5mg/L. In other concentrations there were no significant differences in comparison to the control group. Both the TBO and the MB at 25 mg/L associated with a red laser had an excellent potential for use in PDT in lethal sensitization of S. mutans.
Bhalla, Devender; Tchalla, Achille Edem; Marin, Benoît; Ngoungou, Edgard Brice; Tan, Chong Tin; Preux, Pierre-Marie
Is epilepsy truly an "African ailment"? We aimed to determine this, since international health agencies often refer to epilepsy as an African disease and the scientific literature has spoken the same tone. Various published materials, mainly reports, articles, were used to gather Asian and African evidence on various aspects of epilepsy and many of its risk and associated factors. Our results suggest that in no way can epilepsy be considered as an African ailment and such characterization is most likely based on popular beliefs rather than scientific evidence. In comparison to Africa, Asia has a 5.0% greater burden from all diseases, and is 17.0% more affected from neuropsychiatric disorders (that include epilepsy). Given that more countries in Asia are transitioning, there may be large demographic and lifestyle changes in the near future. However these changes are nowhere close to those expected in Africa. Moreover, 23 million Asians have epilepsy in comparison to 3.3 million Africans and 1.2 million sub-Saharan Africans. In comparison to Africa, Asia has more untreated patients, 55.0% more additional epilepsy cases every year, because of its larger population, with greater treatment cost and possibly higher premature mortality. Of several associated factors discussed herein, many have more importance for Asia than Africa. The current state of epilepsy in Asia is far less than ideal and there is an urgent need to recognize and accept the importance of epilepsy in Asia. In no way can epilepsy be considered as an African ailment. This is most likely based on popular beliefs rather than scientific evidence. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Pogue, Brian W.; Burke, Gregory C.; Lee, Claudia C.; Hoopes, P. Jack
Photodynamic therapy can provide a reliable method of tumor destruction when the appropriate dosimetry is applied. Current dosimetry practice involves quantification of the drug and light doses applied to the tumor, but it would be desirable to monitor in vivo light and drug levels to provide the most accurate determination of dosimetry. In vivo measurements can be used to minimize variations in treatment response due to inter-animal variability, by providing animal-specific or patient-specific treatment planning. This study reports on the development of a micro-sampling method to measure fluorescence from tissue, which is not significantly affected by the tissue optical properties. The system measures fluorescence from the surface of a tissue, using a fiber bundle composed of individual 100 micron fibers which ar all spaced apart by 700 microns from one another at the tissue contact end. This design provides sampling of the fluorescence at multiple sites to increase the signal intensity, while maintaining a micro- sampling of the tissue volume just below the surface. The calibration studies here indicate that the 1/e sampling depth is near 60 microns when measured in optical phantoms, which are similar to typical tissue properties. The probe fluorescence signal is independent of blood concentration up to a maximum of 10% blood by volume, which is similar to most tumor tissue. Animal tests indicate that the sensitivity to drug concentration is essentially the same in when measured in murine liver and muscle tissues, both in vivo and ex vivo. These preliminary calibration results suggest that the probe can be used to measure photosensitizer uptake in vivo non- invasively and rapidly via conversion of fluorescence intensity to photosensitizer concentration.
Elger, Christian E; Johnston, Samantha A; Hoppe, Christian
At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Numerous epilepsy genes have been identified in the last years, mostly in the (rare) monogenic forms and thanks to the increased availability and the decreased cost of next-generation sequencing approaches. Besides the somehow expected group of epilepsy genes encoding various ion channel subunits (e.g. sodium or potassium channel subunits, or GABA receptors, or glutamate-gated NMDA receptors), more diversity has emerged recently, with novel epilepsy genes encoding proteins playing a wide range of physiological roles at the cellular and molecular levels, such as synaptic proteins, members of the mTOR pathway, or proteins involved in chromatin remodeling. The overall picture is somehow complicated: one given epilepsy gene can be associated with more than one epileptic phenotype, and with variable degrees of severity, from the benign to the severe forms (e.g. epileptic encephalopathies), and with various comorbid conditions such as migraine or autism spectrum of disorders. Conversely, one given epileptic syndrome may be associated with different genes, some of which have obvious links with each other (e.g. encoding different subunits of the same receptor) while other ones have no clear relationships. Also genomic copy number variations have been detected, some of which, albeit rare, may confer high risk to epilepsy. Whereas translation from gene identification to targeted medicine still remains challenging, progress in epilepsy genetics is currently revolutionizing genetic-based diagnosis and genetic counseling. Epilepsy gene identification also represents a key entry point to start in deciphering the underlying pathophysiological mechanisms via the design and the study of the most pertinent cellular and animal models - which may in turn provide proofs-of-principle for future applications in human epilepsies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Epilepsy is a heterogeneous clinical condition characterized by recurrent unprovoked seizures, their causes and complications. The incidence, prevalence and mortality of epilepsy vary with age, place and time contributing to a variable extent to the burden of the disease. Diagnostic misclassification may have strong impact on personal and societal reflections of the disease in light of its clinical manifestations and the need for chronic treatment. Epilepsy accounts for a significant proportion of the world's disease burden ranking fourth after tension-type headache, migraine and Alzheimer disease. Among neurological diseases, it accounts for the highest disability-adjusted life year rates both in men and in women. Although epilepsy is self-remitting in up to 50% of cases, variable long-term prognostic patterns can be identified based on the response to the available treatments. Epilepsy carries an overall increased risk of premature mortality with variable estimates across countries. Premature mortality predominates in patients aged less than 50 years, with epilepsies due to structural/metabolic conditions, with generalized tonic-clonic seizures, and seizures not remitting under treatment. Among deaths directly attributable to epilepsy or seizures, included are sudden unexpected death in epilepsy (SUDEP), status epilepticus, accidents, drowning, unintentional injuries, and suicide. Somatic and psychiatric disorders prevail in patients with epilepsy than in people without epilepsy. Asthma, migraine and cerebral tumors tend to occur more frequently in younger adults while cardiovascular disorders, stroke, dementia and meningioma predominate in the elderly. As being a fairly common clinical condition affecting all ages and requiring long-term (sometimes lifelong) treatment, epilepsy carries high health care costs for the society. Direct costs peak in the first year after diagnosis and then vary according to the severity of the disease, the response to treatment, and
Kinariwalla, Neha; Sen, Arjune
There have been many studies exploring quality of life as well as the impact of epilepsy on the affected individual. However, epilepsy affects more than the patients themselves, and there seems to be a paucity of data regarding the impact of epilepsy beyond the person with epilepsy (PWE). In particular, it is uncertain what the impact of epilepsy on marriage may be. We therefore performed a narrative review to evaluate work measuring the psychosocial effect of epilepsy on marriage. We reviewed the literature on epilepsy and marriage by searching PubMed (Medline) and EMBASE and thoroughly examining relevant bibliographies. Forty-two papers were identified that addressed the issue of the psychosocial effect of epilepsy on marriage. The different approaches used to assess the impact of epilepsy on marriage can be broadly grouped into three categories: assessment of the social effect of living with epilepsy, which includes the marital prospects of PWEs and how changes in martial status associate with seizure frequency; assessment of quality of life (QOL) of PWEs; assessment of the association of social support with the disease burden of epilepsy. Within each of these approaches, different research methods have been employed including questionnaires, qualitative methods, and scales. The studies reviewed indicate that epilepsy has a severe impact on individuals and their families. While many quality-of-life surveys do comment on the marital status of the patient, there is little expansion beyond this. The impact that seizures may have on the partner of a patient with epilepsy is barely addressed. With increasing incidence of epilepsy in older populations, potential changes in the dynamic of a long-term marriage with the development of epilepsy in older age are not known. Similarly, the impact of marriage on concordance with medication or proceeding to, for example, surgical treatment for pharmacoresistant epilepsy has not been studied in detail. We suggest ways in which
Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.
Photodynamic Therapy (PDT) is an optical treatment modality that allows malignant tissue destruction. It is based on the administration of a photosensitizer and the posterior irradiation by an optical source. Photosensitizer molecules absorb the excitation light photons triggering a series of photochemical reactions in the presence of oxygen in the target tissue. During such interactions it is produced the de-excitation of the photosensitizer molecules in the singlet excited state which return to their minimum energy state by emitting fluorescence photons. These days, there are fixed clinical PDT protocols that make use of a particular optical dose and photosensitizer amount. However treatment response varies among patients and the type of pathology. In order to adjust an optimal dosimetry, the development of accurate predictive models plays an important role. The photosensitizer fluorescence can be used to estimate the degradation of the photoactive agent and as an implicit dosimetric measurement during treatment. However it is complex to know the fluorescence dependence with the depth in the tumor from observed fluorescence in the pathology surface. We present a first approach to predict the photosensitizer fluorescence dependence with depth during the PDT treatment applied to a skin disease commonly treated in the dermatological clinical practice. The obtained results permit us to know the photosensitizer temporal fluorescence evolution in different points of the tumor sample during the photochemical reactions involved in PDT with a predictive purpose related to the treatment evolution. The model presented also takes into account the distribution of a topical photosensitizer, the propagation of light in a biological media and the subsequent photochemical interactions between light and tissue. This implies that different parameters related with the photosensitizer distribution or the optical source characteristics could be adjusted to provide a specific treatment
Brook, Heather A.; Hiltz, Cynthia M.; Kopplin, Vicki L.; Lindeke, Linda L.
A high prevalence of epilepsy diagnoses and seizure events among students was identified at a large Midwestern school district. In partnership with the Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was conducted to provide education and resources to staff caring for school children with seizures. School nurses (N = 26)…
Malow, Beth A
The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum disorders. Epilepsy and sleep have reciprocal relationships, with sleep facilitating seizures and seizures adversely affecting sleep architecture. The hypothesis put forth is that identifying and treating sleep disorders, which are potentially caused by or contributed to by autism, may impact favorably on seizure control and on daytime behavior. The article concludes with some practical suggestions for the evaluation and treatment of sleep disorders in this population of children with autism.
Johnston, J A; Rees, M I; Smith, P E M
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
Goldman, Alica M.
The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…
Virginia Univ., Charlottesville. Comprehensive Epilepsy Program.
The paper describes the Comprehensive Epilepsy Program at the University of Virginia Medical Center and includes information on the following topics: basic questions about epilepsy; describing and recording seizure activity; first aid in seizure care; the inpatient and outpatient educational service component; admission and referral; international…
Hitiris, Nikolas; Mohanraj, Rajiv; Norrie, John; Brodie, Martin J
All studies report an increased mortality risk for people with epilepsy compared with the general population. Population-based studies have demonstrated that the increased mortality is often related to the cause of the epilepsy. Common etiologies include neoplasia, cerebrovascular disease, and pneumonia. Deaths in selected cohorts, such as sudden unexpected death in epilepsy (SUDEP), status epilepticus (SE), suicides, and accidents are more frequently epilepsy-related. SUDEP is a particular cause for concern in younger people, and whether and when SUDEP should be discussed with patients with epilepsy remain problematic issues. Risk factors for SUDEP include generalized tonic-clonic seizures, increased seizure frequency, concomitant learning disability, and antiepileptic drug polypharmacy. The overall incidence of SE may be increasing, although case fatality rates remain constant. Mortality is frequently secondary to acute symptomatic disorders. Poor compliance with treatment in patients with epilepsy accounts for a small proportion of deaths from SE. The incidence of suicide is increased, particularly for individuals with epilepsy and comorbid psychiatric conditions. Late mortality figures in patients undergoing epilepsy surgery vary and are likely to reflect differences in case selection. Future studies of mortality should be prospective and follow agreed guidelines to better quantify risk and causation in individual populations.
Peljto, Anna L.; Barker-Cummings, Christie; Vasoli, Vincent M.; Leibson, Cynthia L.; Hauser, W. Allen; Buchhalter, Jeffrey R.
Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935–94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives’ medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75–5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted ‘prenatal/developmental cause’ (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as ‘idiopathic’ or ‘unknown cause’), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93–15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92–4.00) for focal epilepsy. In relatives of
Pennell, Page B.
Synopsis The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis. Common symptoms include sexual dysfunction, decreased fertility, premature menopause, and polycystic ovarian syndrome. Antiepileptic drugs and hormones have a bidirectional interaction, with a decrease in the efficacy of hormonal contraceptive agents with some AEDs and a decrease in the concentration and efficacy of other AEDs with hormonal contraceptives. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this knowledge can be used to develop hormonal strategies to improve seizure control in people with epilepsy. PMID:19853217
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.
Zubkov, Sarah; Friedman, Daniel
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.
Arts, Willem F. M.; Brouwer, Oebele F.; Peters, A. C. Boudewijn; Stroink, Hans; Peeters, Els A. J.; Schmitz, Paul I. M.; van Donselaar, Cees A.; Geerts, Ada T.
Knowing the prognosis of epilepsy will undoubtedly influence the treatment strategy. This study aimed to define the prospects of newly diagnosed childhood epilepsy, assess the dynamics of its course, identify relevant variables and develop models to assess the individual prognosis. Four hundred and fifty-three children with newly diagnosed…
Varley, Jarlath; Delanty, Norman; Normand, Charles; Coyne, Imelda; McQuaid, Louise; Collins, Claire; Boland, Michael; Grimson, Jane; Fitzsimons, Mary
Epilepsy is a chronic neurological disease affecting people of every age, gender, race and socio-economic background. The diagnosis and optimal management relies on contribution from a number of healthcare disciplines in a variety of healthcare settings. To explore the interface between primary care and specialist epilepsy services in Ireland. Using appreciative inquiry, focus groups were held with healthcare professionals (n=33) from both primary and tertiary epilepsy specialist services in Ireland. There are significant challenges to delivering a consistent high standard of epilepsy care in Ireland. The barriers that were identified are: the stigma of epilepsy, unequal access to care services, insufficient human resources, unclear communication between primary-tertiary services and lack of knowledge. Improving the management of people with epilepsy requires reconfiguration of the primary-tertiary interface and establishing clearly defined roles and formalised clinical pathways. Such initiatives require resources in the form of further education and training and increased usage of information communication technology (ICT). Epilepsy services across the primary-tertiary interface can be significantly enhanced through the implementation of a shared model of care underpinned by an electronic patient record (EPR) system and information communication technology (ICT). Better chronic disease management has the potential to halt the progression of epilepsy with ensuing benefits for patients and the healthcare system. Copyright 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Mameniskiene, R; Sakalauskaite-Juodeikiene, E; Budrys, V
For people with epilepsy, knowledge of their disease is an important factor in optimizing the control of their seizures. Better-informed patients can more easily participate in the treatment process, reducing disease-related anxiety and coping better with stigma. This study was developed in a Lithuanian tertiary epilepsy center to assess knowledge of disease among people with epilepsy, to estimate differences in disease knowledge between patient groups, and to evaluate how epilepsy influences patients' daily lives. We asked patients to complete a questionnaire and collected information from outpatient cards on epilepsy etiology, type of seizures, findings of diagnostic tests, and information about patients' antiepileptic drugs. Our results showed that people with epilepsy have poor knowledge about their disease: almost half of the patients did not identify the cause of their illness or their type of seizures; most did not know the results of their EEG and neuroimaging studies. Patients also lacked general knowledge about their disease and implications for lifestyle. However, cognitive deficits were not assessed in this study, and this may have affected the answers where patients were required to recall and name their drugs or the dosage of medication. Almost half of them believed that epilepsy had changed their lives significantly and reported anxiety and constant fear of seizures. Patients were also afraid to have because of the possibility they would also have epilepsy. There is clearly a great need for improved educational intervention for people with epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.
Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions
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
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.
Vezzani, Annamaria; Fujinami, Robert S.; White, H. Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W.; Löscher, Wolfgang
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
Forsgren, Lars; Sundelin, Heléne; Sveinsson, Olafur
Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.
Serletis, Demitre; Bulacio, Juan; Alexopoulos, Andreas; Najm, Imad; Bingaman, William; González-Martínez, Jorge
Surgery for frontal lobe epilepsy often has poor results, likely because of incomplete resection of the epileptogenic zone. To present our experience with a series of patients manifesting 2 different anatomo-electro-clinical patterns of refractory orbitofrontal epilepsy, necessitating different surgical approaches for resection in each group. Eleven patients with refractory epilepsy involving the orbitofrontal region were consecutively identified over 3 years in whom stereoelectroencephalography identified the epileptogenic zone. All patients underwent preoperative evaluation, stereoelectroencephalography, and postoperative magnetic resonance imaging. Demographic features, seizure semiology, imaging characteristics, location of the epileptogenic zone, surgical resection site, and pathological diagnosis were analyzed. Surgical outcome was correlated with type of resection. Five patients exhibited orbitofrontal plus frontal epilepsy with the epileptogenic zone consistently residing in the frontal lobe; after surgery, 4 patients were free of disabling seizures (Engel I) and 1 patient improved (Engel II). The remaining 6 patients had multilobar epilepsy with the epileptogenic zone located in the orbitofrontal cortex associated with the temporal polar region (orbitofrontal plus temporal polar epilepsy). After surgery, all 6 patients were free of disabling seizures (Engel I). Pathology confirmed focal cortical dysplasia in all patients. We report no complications or mortalities in this series. Our findings highlight the importance of differentiating between orbitofrontal plus frontal and orbitofrontal plus temporal polar epilepsy in patients afflicted with seizures involving the orbitofrontal cortex. For identified cases of orbitofrontal plus temporal polar epilepsy, a multilobar resection including the temporal pole may lead to improved postoperative outcomes with minimal morbidity or mortality.
Richard, Annie E; Scheffer, Ingrid E; Wilson, Sarah J
Richard, A.E., I.E. Scheffer and S.J. Wilson. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2016. To inform on mechanisms underlying the comorbidity of epilepsy and autism spectrum disorder (ASD), we conducted meta-analyses to test whether impaired facial emotion recognition (FER) and theory of mind (ToM), key phenotypic traits of ASD, are more common in people with epilepsy (PWE) than controls. We contrasted these findings with those of relatives of individuals with ASD (ASD-relatives) compared to controls. Furthermore, we examined the relationship of demographic (age, IQ, sex) and epilepsy-related factors (epilepsy onset age, duration, seizure laterality and origin) to FER and ToM. Thirty-one eligible studies of PWE (including 1449 individuals: 77% with temporal lobe epilepsy), and 22 of ASD-relatives (N=1295) were identified by a systematic database search. Analyses revealed reduced FER and ToM in PWE compared to controls (p<0.001), but only reduced ToM in ASD-relatives (p<0.001). ToM was poorer in PWE than ASD-relatives. Only weak associations were found between FER and ToM and epilepsy-related factors. These findings suggest shared mechanisms between epilepsy and ASD, independent of intellectual disability. Copyright © 2017 Elsevier Ltd. All rights reserved.
Clin, Benedicte; Stosse-Guevel, Catherine; Marquignon, Marie-France; Verneuil, Laurence; Letourneux, Marc
Eczema associated with bryozoans is a form of occupational dermatosis caused by a living animal, involving contact eczema, occasionally associated with photosensitivity and concerning fishermen on a quasi-elective basis. This affection can prove to be extremely disabling, frequently generating disastrous social consequences, since the eviction of the responsible allergen is very often synonymous to occupational reclassification, a measure which fishermen, highly attached to their profession, have great difficulty in accepting. Based on the description of three cases of photosensitive eczema associated with contact with the bryozoan, Alcyonidium gelatinosum, identified in fishermen from the English Channel coastline, we describe the characteristics and the specificities of this occupational dermatosis, then approach the issue of its prevention, which, unfortunately, remains limited.
Licchetta, Laura; Baldassari, Sara; Palombo, Flavia; Menghi, Veronica; D'Aurizio, Romina; Leta, Chiara; Stipa, Carlotta; Boero, Giovanni; d'Orsi, Giuseppe; Magi, Alberto; Scheffer, Ingrid; Seri, Marco; Tinuper, Paolo; Bisulli, Francesca
Objective: To identify novel genes implicated in epilepsy with auditory features (EAF) in phenotypically heterogeneous families with unknown molecular basis. Methods: We identified 15 probands with EAF in whom an LGI1 mutation had been excluded. We performed electroclinical phenotyping on all probands and available affected relatives. We used whole-exome sequencing (WES) in 20 individuals with EAF (including all the probands and 5 relatives) to identify single nucleotide variants, small insertions/deletions, and copy number variants. Results: WES revealed likely pathogenic variants in genes that had not been previously associated with EAF: a CNTNAP2 intragenic deletion, 2 truncating mutations of DEPDC5, and a missense SCN1A change. Conclusions: EAF is a clinically and molecularly heterogeneous disease. The association of EAF with CNTNAP2, DEPDC5, and SCN1A mutations widens the phenotypic spectrum related to these genes. CNTNAP2 encodes CASPR2, a member of the voltage-gated potassium channel complex in which LGI1 plays a role. The finding of a CNTNAP2 deletion emphasizes the importance of this complex in EAF and shows biological convergence. PMID:27066544
Standard developer solution is mixed with dipropyl carbonate. This reduces swelling in the photosensitive resist and permits application of relatively thick films with minimal pinhole formation and increased line resolution.
Chamorro-Muñoz, María Isabel; García-Martín, Guillermina; Pérez-Errazquin, Francisco; Romero-Acebal, Manuel; García-Rodríguez, Antonio; Gutiérrez-Bedmar, Mario
Studies concerning mortality in epilepsy have been performed primarily in Northern-Central Europe and US. The aim of this study was to provide information about mortality in people with epilepsy in Southern European countries. We studied a Spanish prevalence and incidence cohort of 2309 patients aged ≥14 years with epilepsy who were treated in an outpatient epilepsy clinic between 2000 and 2013. The deceased were identified through Civil Registries. Causes of death were determined using death certificates, forensic autopsies, hospital reports, family practitioners, and care-givers' records. Standardised mortality ratios (SMRs) were calculated. In a total of 15,865 person-years of follow-up, 152 patients died, resulting in an SMR of 2.11 (95% CI 1.79-2.47), which was higher for those aged 14-24. There was also a high rate of death for symptomatic epilepsies, progressive causes (SMR=6.12, CI 3.50-9.94), and remote causes (SMR=2.62, CI 2.12-3.21). High SMRs were found for all kinds of epilepsy and for respiratory and tumoural causes. Patients who died of epilepsy itself were 12.5%. Sudden unexpected death in epilepsy incidence was 0.44:1000. Death from status epilepticus incidence was 20:100,000. SMRs for external causes were of no statistical significance. This is the first epidemiological study to examine rate of mortality in epilepsy in a Southern European country. The identified mortality pattern is similar to the one provided by researchers from developed countries. The similarities between our results concerning epilepsy-related deaths and those provided by population-based studies are the result of the scarcely selected character of our study cohort. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
O'Toole, S; Benson, A; Lambert, V; Gallagher, P; Shahwan, A; Austin, J K
In childhood chronic illness, family communication can impact the child's and parents' psychosocial well-being. However, little is known about family communication in the context of epilepsy in childhood. The aim of this systematic review was to identify the existing evidence available on communication strategies adopted by families living with childhood epilepsy, including; the facilitators, barriers and challenges experienced by families when choosing to communicate, or not, about epilepsy; and the consequences of this communication. Papers published in the English language prior to March 2015 were identified following a search of six electronic databases: PubMed, MEDLINE, Web of Science, PsycINFO, CINAHL, and Scopus. Studies were included if they involved a sample of parents of children with epilepsy or children/young people with epilepsy (0-18years of age) and used qualitative, quantitative, or mixed methods. Following a comprehensive search and screening process, 26 studies were identified as eligible for inclusion in the review. No studies identified specific communication strategies adopted by families living with childhood epilepsy. Some studies found that talking about epilepsy with family members had positive consequences (e.g., communication as an effective coping strategy), with no negative consequences reported in any of the studies. The main barrier to communication for parents was an unwillingness to use the word "epilepsy" because of the perceived negative social connotations associated with the health condition. For children with epilepsy, barriers were as follows: parental desire to keep epilepsy a secret, parents' tendency to deny that the child had epilepsy, parental overprotection, and parents' tendency to impose greater restrictions on the child with epilepsy than on siblings without epilepsy. Future research investigating the communication strategies of families living with epilepsy is needed in order to create effective communication
Williamson, P D; Jobst, B C
Epilepsy surgery (ES) is a well-accepted treatment for medically intractable epilepsy patients in developed countries, but it is highly technology dependent. Such technology is not usually available in developing countries. For presurgical evaluation, magnetic resonance imaging (MRI) and electroencephalogram recording while videotaping the patient have been important. High technology equipment will, in conjunction with MRI, identify approximately 70% of ES candidates. Introducing ES into developing countries will require determining the candidates that are appropriate for the existing medical infrastructure. This article reviews ES and its possible introduction into conditions existing in developing countries. The authors address (a) the types of patients to be considered for resective ES (some patients require a fairly standard series of noninvasive studies: others will require extensive invasive studies), (b) ways to determine which patients might be appropriate for the existing situation (unilateral mesial temporal lobe epilepsy detected with MRI, epilepsy with a circumscribed MRI lesion, hemispheric lesions, circumscribed MRI detected neuronal migration, and development disorders), (c) surgical procedures (local resection, functional hemispherectomy, multiple subpial transections, corpus callosotomy, and implantation of a vagal nerve stimulator), (d) special considerations for introducing ES into developing countries (medical infrastructure, technology, seizure monitoring systems, selective intracarotid/carotid Amytal testing, and surgical equipment), and (e) the limitations, realistic expectations, personnel requirements, and educational function for selected professionals. Delivery of the technology and expertise to perform ES in developing regions of the world is a realizable project, but it would be limited by available technology and existing medical infrastructure. It should be possible in most areas to train local personnel and thereby leave a lasting
Carod-Artal, F J
Eighty-five percent of all epileptics live in tropical regions. Prenatal risk factors, traumatic brain injuries and different parasitic infestations of the central nervous system (CNS) are the reasons behind the high prevalence of epilepsy. This work reviews the main parasitic infestations causing epilepsy in the tropics. Neurocysticercosis is the main cause of focal epilepsy in early adulthood in endemic areas (30-50%). All the phases of cysticerci (viable, transitional and calcified) are associated with epileptic seizures. Anti-cysticercus treatment helps get rid of cysticerci faster and reduces the risk of recurrence of seizures in patients with viable cysts. Symptomatic epilepsy can be the first manifestation of neuroschistosomiasis in patients without any systemic symptoms. The pseudotumoral form can trigger seizures secondary to the presence of granulomas and oedemas in the cerebral cortex. The eggs of Schistosoma japonicum are smaller, reach the CNS more easily and trigger epileptic seizures more frequently. Toxocariasis and sparganosis are other parasitic infestations that can give rise to symptomatic seizures. The risk factors for suffering chronic epilepsy after cerebral malaria are a positive familial history of epilepsy and a history of episodes of fever and cerebral malaria that began with coma or which progressed with multiple, prolonged epileptic seizures. About 20% of patients with cerebral infarction secondary to Chagas disease present late vascular epilepsy as a complication. Very few studies have been conducted to examine the prognosis, risk of recurrence and modification of the natural course of seizures associated with tropical parasitic infestations, except for the case of neurocysticercosis.
Tuft, Mia; Gjelsvik, Bergljot; Nakken, Karl O
In "Epilepsy is Dancing", in Antony and the Johnsons' album "The Crying Light"(2009), the lyrics and accompanying music video depicts an epileptic seizure in which the person is transferred to another beautiful and magical world. This may be called "enchanted epilepsy"; i.e., the experience of epilepsy as deeply nourishing and (positively) transforming, is conveyed not only in the lyrics but also the visual and auditory qualities of the video. The seizure in the video gives associations to Shakespeare's "A Midsummer Night's dream". If epilepsy appears in music lyrics, the focus is mostly on negative aspects of the illness, such as horror, fear and repulsive sexuality associated with the fits [1,2]. Contradictory to these lyrics, Anthony and the Johnsons' song is an example of a positive portrayal of epilepsy. It is open to a multitude of meanings, emotional valence and appraisal of epilepsy. By widening the experiential range associated with epileptic seizures, these lyrics highlight the inherently construed nature of epileptic experience. The song stands out in several ways. First, it describes epilepsy in positive terms, prioritising the euphoric, ecstatic, potentially empowering and enhancing aspects of epileptic seizures. Second, the lyrics and accompanying video point to divine experiences associated with epileptic seizures. Through the lyrics and the music video we are, as an audience, able to sense a snicket of an epileptic seizure, but also the universal experience of loosing control. Copyright © 2015 Elsevier Inc. All rights reserved.
Ladino, Lady Diana; Hunter, Gary; Téllez-Zenteno, José Francisco
The impact of health and disease has led many artists to depict these themes for thousands of years. Specifically, epilepsy has been the subject of many famous works, likely because of the dramatic and misunderstood nature of the clinical presentation. It often evokes religious and even mythical processes. Epilepsy surgical treatment has revolutionized the care of selected patients and is a relatively recent advance. Epilepsy surgery has been depicted in very few artistic works. The first portrait showing a potential surgical treatment for patients with epilepsy was painted in the 12th century. During the Renaissance, Bosch famously provided artistic commentary on traditional beliefs in "The stone of madness". Several of these works demonstrate a surgeon extracting a stone from a patient's head, at one time believed to be the source of all "folly", including epileptic seizures, psychosis, intellectual disability, depression, and a variety of other illnesses. There are some contemporary art pieces including themes around epilepsy surgery, all of them depicting ancient Inca Empire procedures such as trepanning. This article reviews the most relevant artistic works related with epilepsy surgery and also its historical context at the time the work was produced. We also present a painting from the Mexican artist Eduardo Urbano Merino that represents the patient's journey through refractory epilepsy, investigations, and ultimately recovery. Through this work, the artist intends to communicate hope and reassurance to patients going through this difficult process. © 2013.
Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the
Castrén, Maija; Gaily, Eija; Tengström, Carola; Lähdetie, Jaana; Archer, Hayley; Ala-Mello, Sirpa
Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been identified in female patients with early onset epileptic encephalopathy and severe mental retardation with a Rett-like phenotype. Subsequently CDKL5 mutations were shown to be associated with more diverse phenotypes including mild epilepsy and autism without epilepsy. Furthermore, CDKL5 mutations were found in patients with Angelman-like phenotype. The severity of epilepsy associated with CDKL5 mutations was recently shown to correlate with the type of CDKL5 mutations and epilepsy was identified to involve three distinct sequential stages. Here, we describe the phenotype of a severe form of neurodevelopmental disease in a female patient with a de novo nonsense mutation of the CDKL5 gene c.175C > T (p.R59X) affecting the catalytic domain of CDKL5 protein. Mutations in the CDKL5 gene are less common in males and can be associated with a genomic deletion as found in our male patient with a deletion of 0.3 Mb at Xp22.13 including the CDKL5 gene. We review phenotypes associated with CDKL5 mutations and examine putative relationships between the clinical epilepsy phenotype and the type of the mutation in the CDKL5 gene. © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Richter, Anna M.; Jain, Ashok K.; Canaan, Alice J.; Meadows, Howard; Levy, Julia G.
Skin photosensitivity is the most common side effect of photodynamic therapy (PDT) and in clinical situations needs to be avoided or at least minimized. However, because of the accessibility of skin tissue, skin photosensitivity represents a useful test system in vivo for evaluation of the pharmacokinetics of photosensitizers and light sources. Pig skin resembles in many aspects human skin and, therefore, is most suitable for these tests. Using pig skin photosensitivity as an end point, we evaluate the effect of cell loading with a photosensitizer, benzoporphyrin derivative (BPD verteporfin) following its intravenous administration either as a rapid bolus or slow infusion. Skin response to light activation indicated a very similar cell content of BPD. These results were in agrement with those obtained in an in vitro model. In addition, in the same pig skin photosensitivity model we compared the efficiency of activation of BPD with either laser (690 plus or minus 3 nm) or light-emitting diode (LED; 690 plus or minus 12 nm) light. Results indicated the equivalency of the two light sources in this test system, with LED light being slightly more efficient, due possibly to a fluence rate lower than laser light.
Prasmickaite, L; Høgset, A; Berg, K
Many potentially therapeutic macromolecules, e.g. transgenes used in gene therapy, are taken into the cells by endocytosis, and have to be liberated from endocytic vesicles in order to express a therapeutic function. To achieve this we have developed a new technology, named photochemical internalization (PCI), based on photochemical reactions inducing rupture of endocytic vesicles. The aim of this study was to clarify which properties of photosensitizers are important for obtaining the PCI effect improving gene transfection. The photochemical effect on transfection of human melanoma THX cells has been studied employing photosensitizers with different physicochemical properties and using two gene delivery vectors: the cationic polypeptide polylysine and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Photochemical treatment by photosensitizers that do not localize in endocytic vesicles (tetra[3-hydroxyphenyl]porphyrin and 5-aminolevulinic acid-induced protoporphyrin IX) do not stimulate transfection, irrespective of the gene delivery vector. In contrast, photosensitizers localized in endocytic vesicles stimulate polylysine-mediated transfection, and amphiphilic photosensitizers (disulfonated aluminium phthalocyanine [AlPcS2a] and meso-tetraphenylporphynes) show the strongest positive effect, inducing approximately 10-fold increase in transfection efficiency. In contrast, DOTAP-mediated transfection is inhibited by all photochemical treatments irrespective of the photosensitizer used. Neither AlPcS2a nor Photofrin affects the uptake of the transfecting DNA over the plasma membrane, therefore photochemical permeabilization of endocytic vesicles seems to be the most likely mechanism responsible for the positive PCI effect on gene transfection.
Stefanescu, Roxana A; Shivakeshavan, R G; Talathi, Sachin S
Approximately 30% of epilepsy patients suffer from medically refractory epilepsy, in which seizures can not controlled by the use of anti-epileptic drugs (AEDs). Understanding the mechanisms underlying these forms of drug-resistant epileptic seizures and the development of alternative effective treatment strategies are fundamental challenges for modern epilepsy research. In this context, computational modeling has gained prominence as an important tool for tackling the complexity of the epileptic phenomenon. In this review article, we present a survey of computational models of epilepsy from the point of view that epilepsy is a dynamical brain disease that is primarily characterized by unprovoked spontaneous epileptic seizures. We introduce key concepts from the mathematical theory of dynamical systems, such as multi-stability and bifurcations, and explain how these concepts aid in our understanding of the brain mechanisms involved in the emergence of epileptic seizures. We present a literature survey of the different computational modeling approaches that are used in the study of epilepsy. Special emphasis is placed on highlighting the fine balance between the degree of model simplification and the extent of biological realism that modelers seek in order to address relevant questions. In this context, we discuss three specific examples from published literature, which exemplify different approaches used for developing computational models of epilepsy. We further explore the potential of recently developed optogenetics tools to provide novel avenue for seizure control. We conclude with a discussion on the utility of computational models for the development of new epilepsy treatment protocols. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Levy, Julia G.; Hunt, David W. C.; Mitchell, David W.; Jamieson, Catriona H. M.
The effects of the photosensitizers, PhotofrinTM and benozoporphyrin derivative monoacid ring A (BPD) on a variety of hematopoietic cell functions have been studied, both in the presence and absence of light activation. A marked increase in hematopoiesis was observed in the bone marrow and spleens of DBA/2 mice administered high dose Photofrin but not BPD. This was manifested in an increased relative spleen weight, nucleated spleen cell number and circulating white blood cell concentration 7 days following Photofrin injection. We have shown that BPD and light doses just below phototoxic ranges stimulate the growth of human colony forming committed myeloid progenitors as well as pluripotent stem cells grown in long term marrow culture. Studies on the effect of BPD on the function of T lymphocytes in the absence of light has also demonstrated a stimulatory effect. The dose range in which this is observed is considerably broader than that observed with light activation. The mechanisms involved in this stimulatory effect have been studied and are discussed.
Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced 11C-flumazenil (GABAA-cBDZ) and 18F-MPPF (5-HT1A serotonin) and increased 11C-cerfentanil (mu opiate) and 11C-MeNTI (delta opiate) bindings in the area of seizure. 11C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that 11C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous sclerosis complex
Sucksdorff, Dan; Brown, Alan S; Chudal, Roshan; Jokiranta-Olkoniemi, Elina; Leivonen, Susanna; Suominen, Auli; Heinimaa, Markus; Sourander, Andre
Population-based studies have demonstrated an overrepresentation of bipolar disorder (BPD) in individuals with epilepsy. However, few studies have examined the reverse association, i.e. comorbid epilepsy in individuals selected based on BPD diagnosis. No previous population-based study having examined the co-occurrence of BPD and epilepsy has adjusted for parental psychopathology. Such an adjustment is motivated by population-based studies reporting an overrepresentation of various types of parental psychiatric disorders in both BPD and epilepsy. Furthermore, an association between epilepsy in first-degree relatives and BPD has previously only been examined and demonstrated in a small clinical sample. The objective of this study is to examine the associations between parental and comorbid epilepsy and BPD, adjusting for parental psychopathology. This nested case-control study identified 1861 cases with BPD, age up to 25 years, 3643 matched controls, and their parents from Finnish national registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and two-sided significance limits of p<0.05. BPD was associated with comorbid epilepsy (adjusted OR 2.53, 95% CI: 1.73-3.70) but not with parental epilepsy. Epilepsy was found in 3.33% of cases versus 1.29% of controls, 2.69% of cases' parents versus 2.53% of controls' parents. The diagnoses were register-based, not based on standardized procedures with direct ascertainment. An association between BPD and comorbid epilepsy persists even after adjusting for parental psychopathology. Lack of familial clustering of BPD and epilepsy would suggest that the elevated co-occurrence of these disorders is influenced by non-genetic factors. Copyright © 2015 Elsevier B.V. All rights reserved.
Tanti, M J; Marson, A G; Jenkinson, M D
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.
Kun, L N; Ling, L W; Wah, Y W; Lian, T T
This survey of 20,542 Singaporean men born in 1974 studied the clinical features of young men diagnosed with epilepsy on preenlistment screening. All male citizens in Singapore are medically screened at age 18 years before enlistment for compulsory military service. Patients suspected to have epilepsy are then referred to government hospitals for further management. We interviewed the patients and their parents and reviewed their hospital records. Eighty-nine patients with epilepsy were identified, indicating a lifetime prevalence of 4.9/1,000 males by age 18 years. The lifetime prevalence of epilepsy among Chinese, Malays, and Indians were 5.2, 2.8, and 6.4/1,000, respectively; these differences were not statistically significant. The mean age of seizure onset was 11.1 years. Generalized seizures (65.2%) were commoner than partial seizures (34.8%); common seizure types included generalized tonic-clonic seizures (52.8%), complex partial seizures with secondary generalization (24.7%), and myoclonic seizures (5.6%). Common epileptic syndromes included temporal lobe epilepsy (16.9%), juvenile myoclonic epilepsy (5.6%), and frontal lobe epilepsy (2.2%). Eighty-four (94.4%) patients sought medical treatment, and seven (7.9%) patients sought additional traditional treatment. Although 70 (78.7%) patients responded to medication, 14 (15.7%) patients remained refractory to treatment. The lifetime prevalence of epilepsy in young Singaporean men was 4.9/1,000. The majority (65.2%) had generalized seizures. Temporal lobe epilepsy was the commonest (16.9%) defined epilepsy syndrome. More patients with epilepsy (94.4%) sought medical treatment, although 15.7% remained refractory to medication.
Syvertsen, Marte; Nakken, Karl Otto; Edland, Astrid; Hansen, Gunnar; Hellum, Morten Kristoffer; Koht, Jeanette
Epilepsy represents a substantial personal and social burden worldwide. When addressing the multifaceted issues of epilepsy care, updated epidemiologic studies using recent guidelines are essential. The aim of this study was to find the prevalence and causes of epilepsy in a representative Norwegian county, implementing the new guidelines and terminology suggested by the International League Against Epilepsy (ILAE). Included in the study were all patients from Buskerud County in Norway with a diagnosis of epilepsy at Drammen Hospital and the National Center for Epilepsy at Oslo University Hospital. The study period was 1999-2014. Patients with active epilepsy were identified through a systematic review of medical records, containing information about case history, electroencephalography (EEG), cerebral magnetic resonance imaging (MRI), genetic tests, blood samples, treatment, and other investigations. Epilepsies were classified according to the revised terminology suggested by the ILAE in 2010. In a population of 272,228 inhabitants, 1,771 persons had active epilepsy. Point prevalence on January 1, 2014 was 0.65%. Of the subjects registered with a diagnostic code of epilepsy, 20% did not fulfill the ILAE criteria of the diagnosis. Epilepsy etiology was structural-metabolic in 43%, genetic/presumed genetic in 20%, and unknown in 32%. Due to lack of information, etiology could not be determined in 4%. Epilepsy is a common disorder, affecting 0.65% of the subjects in this cohort. Every fifth subject registered with a diagnosis of epilepsy was misdiagnosed. In those with a reliable epilepsy diagnosis, every third patient had an unknown etiology. Future advances in genetic research will probably lead to an increased identification of genetic and hopefully treatable causes of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Blair, Robert D. G.
Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone. PMID:22957241
Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy
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.
Buelow, Janice M; Perkins, Susan M; Johnson, Cynthia S; Byars, Anna W; Fastenau, Philip S; Dunn, David W; Austin, Joan K
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.
Andrade, Danielle M; Bassett, Anne S; Bercovici, Eduard; Borlot, Felippe; Bui, Esther; Camfield, Peter; Clozza, Guida Quaglia; Cohen, Eyal; Gofine, Timothy; Graves, Lisa; Greenaway, Jon; Guttman, Beverly; Guttman-Slater, Maya; Hassan, Ayman; Henze, Megan; Kaufman, Miriam; Lawless, Bernard; Lee, Hannah; Lindzon, Lezlee; Lomax, Lysa Boissé; McAndrews, Mary Pat; Menna-Dack, Dolly; Minassian, Berge A; Mulligan, Janice; Nabbout, Rima; Nejm, Tracy; Secco, Mary; Sellers, Laurene; Shapiro, Michelle; Slegr, Marie; Smith, Rosie; Szatmari, Peter; Tao, Leeping; Vogt, Anastasia; Whiting, Sharon; Carter Snead, O
The transition from a pediatric to adult health care system is challenging for many youths with epilepsy and their families. Recently, the Ministry of Health and Long-Term Care of the Province of Ontario, Canada, created a transition working group (TWG) to develop recommendations for the transition process for patients with epilepsy in the Province of Ontario. Herein we present an executive summary of this work. The TWG was composed of a multidisciplinary group of pediatric and adult epileptologists, psychiatrists, and family doctors from academia and from the community; neurologists from the community; nurses and social workers from pediatric and adult epilepsy programs; adolescent medicine physician specialists; a team of physicians, nurses, and social workers dedicated to patients with complex care needs; a lawyer; an occupational therapist; representatives from community epilepsy agencies; patients with epilepsy; parents of patients with epilepsy and severe intellectual disability; and project managers. Three main areas were addressed: (1) Diagnosis and Management of Seizures; 2) Mental Health and Psychosocial Needs; and 3) Financial, Community, and Legal Supports. Although there are no systematic studies on the outcomes of transition programs, the impressions of the TWG are as follows. Teenagers at risk of poor transition should be identified early. The care coordination between pediatric and adult neurologists and other specialists should begin before the actual transfer. The transition period is the ideal time to rethink the diagnosis and repeat diagnostic testing where indicated (particularly genetic testing, which now can uncover more etiologies than when patients were initially evaluated many years ago). Some screening tests should be repeated after the move to the adult system. The seven steps proposed herein may facilitate transition, thereby promoting uninterrupted and adequate care for youth with epilepsy leaving the pediatric system. Wiley
Gadgil, Pradnya; Udani, Vrajesh
Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery.
Gadgil, Pradnya; Udani, Vrajesh
Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery. PMID:22069423
Fang, Hansun; Gao, Yanpeng; Wang, Honghong; Yin, Hongliang; Li, Guiying; An, Taicheng
Residue from the polycyclic musks (PCMs) in household and personal care products may harm human beings through skin exposure. To understand the health effects of PCMs when exposed to sunlight at molecular level, both experimental and computational methods were employed to investigate the photosensitized oxidation performance of 19 natural amino acids, the most basic unit of life. Results showed that a typical PCM, tonalide, acts as a photosensitizer to significantly increase photo-induced oxidative damage to amino acids. Both common and exceptional transformation pathways occurred during the photosensitization damage of amino acids. Experimental tests further identified the different mechanisms involved. The common transformation pathway occurred through the electron transfer from α amino-group of amino acids, accompanying with the formation of O 2 •- . This pathway was controlled by the electronic density of N atom in α amino-group. The exceptional transformation pathway was identified only for five amino acids, mainly due to the reactions with reactive oxygen species, e.g. 1 O 2 and excited triplet state molecules. Additionally, tonalide photo-induced transformation products could further accelerate the photosensitization of all amino acids with the common pathway. This study may support the protection of human health, and suggests the possible need to further restrict polycyclic musks use. Copyright © 2017 Elsevier Ltd. All rights reserved.
Gulati, Sheffali; Yoganathan, Sangeetha; Chakrabarty, Biswaroop
Epilepsy is defined as two or more unprovoked seizures. Epileptic patients have intellectual disability and behavioral co-morbidities to the tune of up to 25 and 75% respectively. Various factors like underlying etiology, socioeconomic environment at home, age at onset, seizure semiology, seizure descriptors like duration, severity and frequency, therapy related adverse effects secondary to antiepileptic drugs and epilepsy surgery have been implicated for the causation of cognitive and behavioral impairment in epilepsy. Cognitive epilepsy has emerged as a specific entity. This may manifest as a transient behavioral or cognitive change, insidous onset subacute to chronic encephalopathy or more catastrophic in the form of nonconvulsive status epilepticus. Cognitive impairment seen in epileptic children include difficulties in learning, memory, problem solving as well as concept formation. Anxiety, depression and attention deficit hyperkinetic disorders are the most common psychiatric co-morbidities seen. Investigating a child with epilepsy for cognitive and behavioral impairment is difficult as these tests would require cooperation from the patient's side to a significant extent. A rational approach towards treatment would be judicious selection of antiepileptic drugs, treatment of underlying cause, appropriate management of behavioral co-morbidities including psychopharmacotherapy and a trial of immunotherapy (particularly in cognitive epilepsies), wherever appropriate.
Pandya, Neil S; Vrbancic, Mirna; Ladino, Lady Diana; Téllez-Zenteno, José F
Purpose We report the rare case of a patient with intractable epilepsy and escalating aggression, resulting in murder, who had complete resolution of her seizures and explosive behavior following a right temporal lobectomy. Patients and methods We searched the available literature from 1880 to 2013 for cases of epilepsy being used as a court defense for murder and collected information regarding the final sentencing outcomes. We selected 15 papers with a total of 50 homicides. Results We describe the case of a 47-year-old woman with drug-resistant right temporal epilepsy who developed increasing emotional lability, outbursts of anger and escalating violent behavior culminating in a violent murder. The patient was imprisoned while awaiting trial. In the interim, she underwent a successful temporal lobectomy with full resolution of seizures, interictal rage and aggressive behaviors. After the surgery, her charges were downgraded and she was transferred to a psychiatric facility. Conclusion The aggressive behavior associated with epilepsy has been described in the literature for over a century. A link between epilepsy and aggression has been disproportionally emphasized. These patients share some common characteristics: they are usually young men with a long history of epilepsy and lower than average intelligence. The violent act is postictal, sudden-onset, more likely to occur after a cluster of seizures and is usually related with alcohol abuse. PMID:23700367
Pimentel, José; Tojal, Raquel; Morgado, Joana
Epilepsy is one of the commonest neurologic diseases and has always been associated with stigma. In the interest of safety, the activities of persons with epilepsy (PWE) are often restricted. In keeping with this, physical exercise has often been discouraged. The precise nature of a person's seizures (or whether seizures were provoked or unprovoked) may not have been considered. Although there has been a change in attitude over the last few decades, the exact role of exercise in inducing seizures or aggravating epilepsy still remains a matter of discussion among experts in the field. Based mainly on retrospective, but also on prospective, population and animal-based research, the hypothesis that physical exercise is prejudicial has been slowly replaced by the realization that physical exercise might actually be beneficial for PWE. The benefits are related to improvement of physical and mental health parameters and social integration and reduction in markers of stress, epileptiform activity and the number of seizures. Nowadays, the general consensus is that there should be no restrictions to the practice of physical exercise in people with controlled epilepsy, except for scuba diving, skydiving and other sports at heights. Whilst broader restrictions apply for patients with uncontrolled epilepsy, individual risk assessments taking into account the seizure types, frequency, patterns or triggers may allow PWE to enjoy a wide range of physical activities. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Argumosa, A; Herranz, J L
The economic magnitude of epilepsy is determined by its effect on the employment status of the patients, the cost of drug treatment for them and the healthcare system and the repercussion worldwide. Studies of the cost of the disease show that it has economic importance due to the sum of the direct and indirect costs caused by it. In the case of epilepsy, the results of studies in various countries led to the creation of a Commission on Economic Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in Spain may explain the lack of publications on this subject in our country. The percentage of the total cost due to antiepileptic drugs is considerable and will probably increase in the future. The pharmaco-economic evaluation made by cost-benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize costs should serve to use healthcare resources in the most effective manner and justify the rational use of the new antiepileptic drugs. The economic impact of epilepsy is added to the repercussion of the disease itself on the patient and his family. The different distribution of costs in children and adults with epilepsy suggest the need for intervention at an early age to try to reduce the long term economic and personal repercussions. The pharmaco-economic evaluation of the new antiepileptic drugs will make it clear whether their considerable cost is worth paying for their greater effectivity.
Kılınç, Stephanie; van Wersch, Anna; Campbell, Carol; Guy, Alison
The incidence and prevalence of adults diagnosed with epilepsy is higher compared to those diagnosed in childhood, yet the experience of living with adult-onset epilepsy has rarely been examined. Hence, the current study took a phenomenological approach to examining the experience of living with epilepsy following diagnosis in adulthood. Semi-structured interviews were conducted with 39 people from across the UK, diagnosed with epilepsy between the ages of eighteen and sixty, at two points in time, six months apart. Phenomenological analysis identified three central themes: the unpredictability of seizure occurrence; the ripple effect; and re-evaluating the future. Despite the accepted consensus in the epilepsy literature that living and coping with epilepsy becomes more difficult the older a person is diagnosed, the current findings indicated that this is inadequate. Rather, it is more suitable to consider that those living with adult-onset epilepsy have a specific experience of the condition and particular support needs, given that they once lived their lives as people without epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.
Myers, Kenneth A; Scheffer, Ingrid E
Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.
Akhavan, S.; Uran, C.; Bozok, B.; Gungor, K.; Kelestemur, Y.; Lesnyak, V.; Gaponik, N.; Eychmüller, A.; Demir, H. V.
We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the current-matching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of single monolayers of colloidal water-soluble CdTe and CdHgTe nanocrystals (NCs) in adjacent junctions on a Kapton polymer tape. Owing to the usage of a single NC layer in each junction, noise generation was significantly reduced while keeping the resulting PNS films considerably transparent. In each junction, photogenerated excitons are dissociated at the interface of the semi-transparent Al electrode and the NC layer, with holes migrating to the contact electrode and electrons trapped in the NCs. As a result, the tandem PNSs lead to an open-circuit photovoltage buildup equal to the sum of those of the two single junctions, exhibiting a total voltage buildup of 128.4 mV at an excitation intensity of 75.8 μW cm-2 at 350 nm. Furthermore, we showed that these flexible PNSs could be bent over 3.5 mm radius of curvature and cut out in arbitrary shapes without damaging the operation of individual parts and without introducing any significant loss in the total sensitivity. These findings indicate that the NC skins are promising as building blocks to make low-cost, flexible, large-area UV/visible sensing platforms with highly efficient full-spectrum conversion.We proposed and demonstrated the first account of large-area, semi-transparent, tandem photosensitive nanocrystal skins (PNSs) constructed on flexible substrates operating on the principle of photogenerated potential buildup, which avoid the need for applying an external bias and circumvent the current-matching limitation between junctions. We successfully fabricated and operated the tandem PNSs composed of
Zhao, Jianzhang; Wu, Wanhua; Sun, Jifu; Guo, Song
Triplet photosensitizers (PSs) are compounds that can be efficiently excited to the triplet excited state which subsequently act as catalysts in photochemical reactions. The name is originally derived from compounds that were used to transfer the triplet energy to other compounds that have only a small intrinsic triplet state yield. Triplet PSs are not only used for triplet energy transfer, but also for photocatalytic organic reactions, photodynamic therapy (PDT), photoinduced hydrogen production from water and triplet-triplet annihilation (TTA) upconversion. A good PS should exhibit strong absorption of the excitation light, a high yield of intersystem crossing (ISC) for efficient production of the triplet state, and a long triplet lifetime to allow for the reaction with a reactant molecule. Most transition metal complexes show efficient ISC, but small molar absorption coefficients in the visible spectral region and short-lived triplet excited states, which make them unsuitable as triplet PSs. One obstacle to the development of new triplet PSs is the difficulty in predicting the ISC of chromophores, especially of organic compounds without any heavy atoms. This review article summarizes some molecular design rationales for triplet PSs, based on the molecular structural factors that facilitate ISC. The design of transition metal complexes with large molar absorption coefficients in the visible spectral region and long-lived triplet excited states is presented. A new method of using a spin converter to construct heavy atom-free organic triplet PSs is discussed, with which ISC becomes predictable, C60 being an example. To enhance the performance of triplet PSs, energy funneling based triplet PSs are proposed, which show broadband absorption in the visible region. Applications of triplet PSs in photocatalytic organic reactions, hydrogen production, triplet-triplet annihilation upconversion and luminescent oxygen sensing are briefly introduced.
Guekht, Alla; Hauser, W Allen; Milchakova, Larissa; Churillin, Yury; Shpak, Alexander; Gusev, Eugene
This study is the first analysis of the epidemiology of epilepsy in the Russian Federation (RF), in the English medical literature. The RF is geographically the largest territory in the world with a population of 142 million. The study evaluated prevalence of epilepsy in older teenagers and adults in 14 regions of the RF with total population of 517,624 persons (about 0.34% of all the population of the RF). Study sites were located in both European (Western population) and Siberian (Eastern population) regions of Russia. We identified 1753 patients with established epilepsy (1033 men, 720 women) from available medical information sources. Epilepsy cases were evaluated by study neurologists or epileptologists; all the patients underwent EEG, one third - neuroimaging. The age adjusted prevalence of epilepsy, standardized to the European Standard Million was 3.40 (95%CI: 3.26-3.55) per 1000. Prevalence was higher among men-4.50 (95%CI: 4.25-4.76) than among women-2.52 (95%CI: 2.35-2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population. The highest prevalence was found in the age group 50-59 years. Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority (81.6%). In about one-third of those with localization-related epilepsies etiology remained undetermined. Head injury was the main identified cause of epilepsy, followed by cerebrovascular disorders. The prevalence of epilepsy in the population ≥ 14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. Copyright © 2010 Elsevier B.V. All rights reserved.
Pembroke, Sinead; Higgins, Agnes; Pender, Niall; Elliott, Naomi
Proponents of resilience theory have highlighted the importance of understanding the processes of resilience. The objective of the study was to explore how people with epilepsy reach a stage of being comfortable with their epilepsy. Identifying the processes used is important to developing effective self-management for people who are newly diagnosed with epilepsy. A grounded theory approach involving forty-nine consenting adult people with epilepsy (18 years and over), was used to explore their first-hand experiences of coming to terms with their epilepsy. Data were collected using one-to-one interview to elicit in-depth personal accounts of people with epilepsy's experiences of adjusting to their diagnosis of epilepsy. Using grounded theory's systematic inductive-deductive process data of analysis, the core findings that emerged from the open coding and inductive phase were analyzed independently by two researchers to ensure that findings were verified and validated across the interview dataset. Three core categories emerged as central to the journey that people experience after receiving their diagnosis of epilepsy towards becoming comfortable with their epilepsy. These were: i) meaning of "my" epilepsy diagnosis, to capture people with epilepsy's feelings, reactions and concerns after being diagnosed with epilepsy, ii) useful strategies, to identify what people with epilepsy did to become comfortable with their diagnosis, and iii) being comfortable with my epilepsy, to account for the frame of mind of people with epilepsy when they reach a point of accepting their diagnosis. The findings provide important insights into the personal experiences of people with epilepsy after receiving their diagnosis and identifies a range of strategies they find useful in helping them reach a position of acceptance and being 'comfortable with my epilepsy'. Copyright © 2017 Elsevier Inc. All rights reserved.
Colebunders, Robert; Tepage, Floribert; Rood, Ente; Mandro, Michel; Abatih, Emmanuel Nji; Musinya, Gisele; Mambandu, Germain; Kabeya, José; Komba, Michel; Levick, Bethany; Mokili, John L; Laudisoit, Anne
Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. Objective To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC). Design/Methods An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran’s I statistic of spatial auto-correlation. Results Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)–the vector of Onchocerca volvulus–oviposit and breed. Conclusions The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy. PMID:27139245
Thurman, David J; Logroscino, Giancarlo; Beghi, Ettore; Hauser, W Allen; Hesdorffer, Dale C; Newton, Charles R; Scorza, Fulvio Alexandre; Sander, Josemir W; Tomson, Torbjörn
Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Lozovskaia, E L; Makareeva, E N; Makedonov, I U
Photosensitizing and photoprotecting efficiency of about a hundred of compounds, mainly drugs, was studied. The method based on chemiluminescence occurred along with photooxidation of glycyltryptophan under irradiation in UVB range in solution was used for testing. As a measure of photosensitizing efficiency the concentration of photosensitizer which induced two-fold increase of chemiluminescence intensity was chosen. The most effective photosensitizers are riboflavin, FAD, furagin, psoralene, vicasol, benzobarbital, mydocalm, angelicyn, furadonin, ethacridin, diazolin, folic acid. With regard to pharmacological doses of drugs in organism more dangerous sensitizers (in descending order) are p-aminosalicylic acid, furagin, riboflavin, benzobarbital, thiopental, chloramphenicol, nicodin, mydocalm, furadonin, oxolonic acid, furazolidone, psoralene, nicotinamide and diazolin. Photoprotecting effect was described by the concentration at which chemiluminescence intensity decreased twice. The most effective photoprotectors are etamsilat, quercetin, ftivazid, chlorpromazine, diprazine, thioridazine, aminophenazone, oxaphenamide. Concentration dependence for some of these drugs (etamsilat, chlorpromazine, diprazine, thioridazine) is non-monotonous: they inhibit photooxidation in low concentration (about 10(-7)-10(-6) M), but at higher concentrations (10(-5)-10(-4) M) photosensitization dominates over photoprotection.
Wirrell, Elaine C
Only one prospective, controlled study has compared the risk of accidental injury in persons with epilepsy to controls without seizures. A mildly increased risk in the epilepsy group was found, predominantly due to injuries that result directly from a seizure. With regard to injury type, this study found significantly higher rates of only head and soft tissue injury; however, most injuries were minor. Several retrospective, population-based studies have suggested increased rates of more serious injury types. Submersion injury has a high mortality; the risk of submersion in children with epilepsy is 7.5-13.9 fold higher than in the general population. The risk of fracture is elevated approximately twofold, either resulting directly from seizure-induced injury or predisposed by drug-induced reduction in bone mineral density. Burns due to seizures account for between 1.6% and 3.7% of burn unit admissions. The risk of motor vehicle accidents in drivers with epilepsy also appears increased, albeit marginally. Several factors predispose to a higher risk of injury among those with epilepsy. Seizures resulting in falls increase the risk of concussion and other injuries. Higher seizure frequency, lack of a prolonged seizure-free interval, comorbid attention deficit disorder, or cognitive handicap may also increase the risk of injury. While some restrictions are necessary to protect the safety of the person with epilepsy, undue limitations may further limit achievement of independence. Given the high morbidity and mortality of submersion injury, those with active epilepsy should bathe or swim only with supervision; however, showering is a reasonable option. Appropriate vitamin D and calcium supplementation and periodic measurement of bone mineral density in those at risk for osteopenia are recommended.
Lekoubou, Alain; Bishu, Kinfe G; Ovbiagele, Bruce
The purpose of this study was to evaluate health care expenditures among elderly patients with epilepsy in the United States. We performed an analysis of weighted 37 738 607 US participants aged 65 years to estimate health care expenditures in the elderly with and without epilepsy using the Medical Expenditure Panel Survey Household Component, with 2003-2014 data. Unadjusted health care expenditures were estimated. Independent health care expenditures were estimated, using a 2-part model. We identified 416 496 (1.1%) older individuals with epilepsy. Comorbidities were more prevalent among older individuals with epilepsy versus younger individuals. Mean unadjusted yearly medical cost of epilepsy in elderly patients with epilepsy was $18 712 (95% confidence interval [CI] = $15 947-$21 476) during the pooled period 2003-2014, which was nearly double the equivalent cost in elderly subjects without epilepsy at $10 168 (95% CI = $9925-$10 410). Mean unadjusted annual medical cost of epilepsy in the elderly increased by $2135 from $15 850 (95% CI = $10 668-$21 032) in 2003-2006 to $17 985 (95% CI = $13 710-$22 260) in 2011-2014. Adjusted mean total health care expenditures per person per year for elderly patients with epilepsy were $12 526 in 2003-2006, $13 423 in 2007-2010, and $10 569 in 2011-2014. Adjusted incremental health care costs associated with epilepsy in the elderly accrued by $4595 (95% CI = $2399-$6791) when compared to elderly subjects without epilepsy. We estimated the mean annual aggregate cost of epilepsy at $7.8 billion to the US population. Epilepsy is common among elderly individuals, and health care expenditures among this growing group are 2 times higher than in those without epilepsy. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.
Modi, Avani C; Schmidt, Matthew; Smith, Aimee W; Turnier, Luke; Glaser, Noah; Wade, Shari L
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.
Korenke, Georg-Christoph; Eggert, Marlene; Thiele, Holger; Nürnberg, Peter; Sander, Thomas; Steinlein, Ortrud K
Mutations in NPRL3, one of three genes that encode proteins of the mTORC1-regulating GATOR1 complex, have recently been reported to cause cortical dysplasia with focal epilepsy. We have now analyzed a multiplex epilepsy family by whole exome sequencing and identified a frameshift mutation (NM_001077350.2; c.1522delG; p.E508Rfs*46) within exon 13 of NPRL3. This truncating mutation causes an epilepsy phenotype characterized by early childhood onset of mainly nocturnal frontal lobe epilepsy. The penetrance in our family was low (three affected out of six mutation carriers), compared to families with either ion channel- or DEPDC5-associated familial nocturnal frontal lobe epilepsy. The absence of apparent structural brain abnormalities suggests that mutations in NPRL3 are not necessarily associated with focal cortical dysplasia but might be able to cause epilepsy by different, yet unknown pathomechanisms. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Kimura, Shigemi; Ozasa, Shiro; Nakamura, Kyoko; Nomura, Keiko; Kosuge, Hirofumi
Myoclonic epilepsy associated with ragged-red fibers is one of the mitochondrial encephalomyopathies. Pathogenic mitochondrial DNA mutations have been identified in the mitochondrial transfer RNA (tRNA)(Lys) at positions 8344 and 8356. Characteristics of myoclonic epilepsy associated with ragged-red fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance, lactic acidosis, and ragged-red fibers. The elevated lactate level is one of the most important symptoms needed to make a diagnosis of mitochondrial encephalomyopathy. In the present case, however, myoclonic epilepsy was associated with ragged-red fibers but without increased lactate levels. Therefore, myoclonic epilepsy associated with ragged-red fibers should be suspected in a patient who has myoclonic epilepsy that is difficult to control with antiepileptic medications and who has other symptoms of mitochondrial disease, such as mental retardation, even if the patient's lactate level is normal.
Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F
The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
Vignoli, Aglaia; La Briola, Francesca; Turner, Katherine; Scornavacca, Giulia; Chiesa, Valentina; Zambrelli, Elena; Piazzini, Ada; Savini, Miriam Nella; Alfano, Rosa Maria; Canevini, Maria Paola
Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable, and the reasons for this variability are still controversial. We reviewed the clinical characteristics of patients with TSC who were regularly followed since 2000 at the San Paolo Multidisciplinary Tuberous Sclerosis Centre in Milan, Italy. From patient charts we collected data about age at epilepsy onset, seizure frequency and seizure type, history of infantile spasms (IS), epileptic syndrome, evolution to refractory epilepsy or to seizure freedom and/or medication freedom, electroencephalography (EEG) features, magnetic resonance imaging (MRI) findings, cognitive outcome, and genetic background. Among the 160 subjects (120 adults and 40 children), 116 (72.5%) had epilepsy: 57 (35.6%) were seizure-free, and 59 (36.9%) had drug-resistant epilepsy. Most seizure-free patients had a focal epilepsy (89.5%), with 54.4% of them drug resistant for a period of their lives. Epilepsy onset in the first year of life with IS and/or focal seizures was characteristic of the drug-resistant group of patients, as well as cognitive impairment and TSC2 mutation (p < 0.05). A small group of patients (7 patients, 4.4%) experienced a seizure only once; all of them had normal cognition. Although epilepsy management can be challenging in TSC, more than one third of patients had their seizures controlled: through monotherapy in 56% and by polytherapy in 32%. Moreover, 12% of the patients became seizure-free and were off medication. Identifying predictive features of epilepsy and cognitive outcome can ensure better management for patients with TSC and delineate genotype-phenotype correlations. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Rajapakse, Thilinie; Buchhalter, Jeffrey
gains in understanding, improved classification methods are required to identify and further study these interrelated conditions and move towards improved diagnosis and treatment of disorders on the migraine-epilepsy continuum in children. © 2016 American Headache Society.
Sajobi, Tolulope T; Jette, Nathalie; Fiest, Kirsten M; Patten, Scott B; Engbers, Jordan D T; Lowerison, Mark W; Wiebe, Samuel
Seizure-related disability is an important contributor to health-related quality of life in persons with epilepsy. Yet, there is little information on patient-centered reports of seizure-related disability, as most studies focus on specific constructs of health-related disability, rather than epilepsy. We investigated how patients rate their own disability and how these ratings correlate with various clinical and sociodemographic characteristics. In a prospective cohort of 250 adults with epilepsy consecutively enrolled in the Neurological Disease and Depression Study (NEEDs), we obtained a broad range of clinical and patient-reported measures, including patients' ratings of seizure-related disability and epilepsy severity using self-completed, single-item, 7-point response global assessment scales. Spearman's correlation, multiple linear regression, and mediation analyses were used to examine the association between seizure-related disability scores and clinical and demographic characteristics of persons with epilepsy. The mean age and duration of epilepsy was 39.8 and 16.7 years, respectively. About 29.5% of the patients reported their seizures as "not at all disabling," whereas 5.8% of the patients reported them as "extremely disabling." Age, seizure freedom at 1 year, anxiety, and epilepsy severity were identified as statistically significant predictors of disability scores. The indirect effects of age and seizure freedom, attributable to mediation through epilepsy severity, accounted for 25.0% and 30.3% of the total effects of these determinants on seizure-related disability, respectively. Measuring seizure-related disability has heuristic value and it has important correlates and mediators that can be targeted for intervention in practice. Addressing modifiable factors associated with disability (e.g., seizure freedom and anxiety) could have a significant impact on decreasing the burden of disability in people with epilepsy. Wiley Periodicals, Inc. © 2015
Hun, Chamroeun; Hok, Tola; Ros, Sina; Chan, Samleng; Bhalla, Devender
Epilepsy-related health outcomes remain unacceptably low in much of the developing world. According to us, it is because of the failure since long to see, and address, epilepsy beyond its preset conventional image. The objective of this paper was to highlight the presence, and influence, of these conventional practices and also to demonstrate what happened when a bold unconventional approach to address epilepsy was taken in Cambodia. Data are taken from existing published literature on epilepsy as well as our field experience during several population-based surveys conducted in Cambodia. We complimented this with our knowledge gained over this long period. It is demonstrated that epilepsy is far more important in Asia that it is currently considered to be, and also vis-à-vis other geographic regions. Pregnancy and birth-related factors carry far higher odds for epilepsy than several "highly vocal" infections. A refocus in epilepsy is required to help move from its traditional negative image to an image where epilepsy is considered a "positive-looking" disorder that is full of "opportunities;" such as availability of safe effective inexpensive treatment, etc. Stigma is a two-side entity (i.e., it is present, and it is influential), and diligence should be therefore practiced before using the stigma label. Nevertheless, psychosocial aspects shouldn't be limited to stigma or Jacoby stigma scale alone. Quality of life is a subjective phenomenon, and patients should determine directly what affects them. It is highly desirable that if we want to find newer answers to old problems in epilepsy, we need to shed our conventional approach and preset conclusions. We should choose to move toward "opportunities" visibly present in epilepsy. Our Cambodian experience demonstrates more intimately that opportunities do get identified when preset conclusions are questioned, and an approach that goes beyond expected and by default is taken.
Corral Arroyo, P.; Gonzalez, L.; Steimer, S.; Aellig, R.; Volkamer, R. M.; George, C.; Bartels-Rausch, T.; Ammann, M.
Reactions promoted by light are key in atmospheric chemistry. Some of them occur in the condensed phase of aerosols containing light absorbing organic compounds (George et al., 2015). This work explores the radical reactions initiated by near-UV light in mixtures of citric acid (CA) and imidazole-2-carboxaldehyde (IC) using NO as a probe molecule for HO2, by means of coated wall flow tube experiments. Citric acid may act as H atom or electron donor in condensed phase radical cycles. IC may act as a photosensitizer. The loss of NO was measured by a chemiluminescence detector. The dependence of the NO loss on the NO concentration, the IC/CA ratio in the film, relative humidity, light intensity, oxygen molar fraction were investigated as well as the HONO and NO2 yields. We also added halide salts to investigate the effect of a competing electron donor in the system and the output of halogens to the gas phase. We found a correlation between the loss of NO above the film and the molar ratio of IC/CA and the light intensity. The variation of the NO loss with oxygen corroborates a mechanism, in which the triplet excited state of IC is reduced by citric acid, to a reduced ketyl radical that transfers an electron to molecular oxygen, which in turn leads to production of HO2 radicals. Therefore, the NO loss in the gas phase is related to the production of HO2 radicals. Relative humidity had a strong impact on the HO2 output, which shows a maximum production rate at around 30%. The addition of halide ions (X- = Cl-, Br-, I-) increases the HO2 output at low concentration and decrease it at higher concentration when X2- radical ions likely scavenge HO2. We could preliminarily quantify for the first time the contribution of these processes to the oxidative capacity in the atmosphere and conclude that their role is significant for aerosol aging and potentially a significant source of halogen compounds to the gas phase.
Bacellar, Isabel O L; Baptista, Mauricio S; Junqueira, Helena C; Wainwright, Mark; Thalmann, Fabrice; Marques, Carlos M; Schroder, André P
The modification of lipid bilayer permeability is one of the most striking yet poorly understood physical transformations that follow photoinduced lipid oxidation. We have recently proposed that the increase of permeability of photooxidized 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers is controlled by the time required by the oxidized lipid species to diffuse and aggregate into pores. Here we further probe this mechanism by studying photosensitization of DOPC membranes by methylene blue (MB) and DO15, a more hydrophobic phenothiazinium photosensitizer, under different irradiation powers. Our results not only reveal the interplay between the production rate and the diffusion of the oxidized lipids, but highlight also the importance of photosensitizer localization in the kinetics of oxidized membrane permeability. Copyright © 2018. Published by Elsevier B.V.
Berg, Anne T; Baca, Christine B; Loddenkemper, Tobias; Vickrey, Barbara G; Dlugos, Dennis
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.
Sauro, Khara M; Wiebe, Samuel; Dunkley, Colin; Janszky, Jozsef; Kumlien, Eva; Moshé, Solomon; Nakasato, Nobukazu; Pedley, Timothy A; Perucca, Emilio; Senties, Horacio; Thomas, Sanjeev V; Wang, Yuping; Wilmshurst, Jo; Jetté, Nathalie
The International League Against Epilepsy (ILAE) Epilepsy Guidelines Task Force, composed of 14 international members, was established in 2011 to identify, using systematic review methodology, international epilepsy clinical care guidelines, assess their quality, and determine gaps in areas of need of development. A systematic review of the literature (1985-2014) was performed in six electronic databases (e.g. Medline, Embase) using a broad search strategy without initial limits to language or study design. Six gray literature databases (e.g., American Academy of Neurology [AAN], ILAE) were also searched to minimize publication bias. Two independent reviewers screened abstracts, reviewed full text articles, and performed data abstraction. Descriptive statistics and a meta-analysis were generated. The search identified 10,926 abstracts. Of the 410 articles selected for full text review, 63 met our eligibility criteria for a guideline. Of those included, 54 were in English and 9 were in other languages (French, Spanish, and Italian). Of all guidelines, 29% did not specify the target age groups, 27% were focused on adults, 22% included only children, and 6% specifically addressed issues related to women with epilepsy. Guidelines included in the review were most often aimed at guiding clinical practice for status epilepticus (n = 7), first seizure (n = 6), drug-resistant epilepsy (n = 5), and febrile seizures (n = 4), among others. Most of the guidelines were therapeutic (n = 35) or diagnostic (n = 16) in nature. The quality of the guidelines using a 1-7 point scale (7 = highest) varied and was moderate overall (mean = 4.99 ± 1.05 [SD]). We identified substantial gaps in topics (e.g., epilepsy in the elderly) and there was considerable heterogeneity in methodologic quality. The findings should offer a valuable resource for health professionals caring for people with epilepsy, since they will help guide the prioritization, development, and dissemination of future
Jackson, Cerian F; Makin, Selina M; Baker, Gus A
Many people with epilepsy report experiencing psychological difficulties such as anxiety, depression and neuropsychological deficits including memory problems. Research has shown that these difficulties are often present not only for people with chronic epilepsy but also for people with newly diagnosed epilepsy. Despite this, there are very few published interventions that detail means to help people with newly diagnosed epilepsy manage these problems. To identify and assess possible psychological and neuropsychological interventions for adults with newly diagnosed epilepsy. We searched the following databases on 30 June 2015: the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), SCOPUS, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). This review includes all randomised controlled trials, quasi-randomised controlled trials, prospective cohort controlled studies, and prospective before and after studies which include psychological or neuropsychological interventions for people with newly diagnosed epilepsy. We excluded studies that included people with epilepsy and any other psychological disorder or neurological condition. We excluded studies carried out which recruited only children. We used the standard methodological procedure expected by The Cochrane Collaboration. Two authors independently completed data extraction and risk of bias analysis. The results of this were cross-checked and third author resolved any discrepancies. In the event of missing data, we contacted the study authors. Meta-analysis was not completed due to differences in the intervention and outcomes reported in the two studies. We included two randomised controlled trials assessing psychological interventions for people with newly diagnosed epilepsy. One study assessed a cognitive behavioural intervention (CBI) in an adolescent
Hansen, Julia; Åsberg, Signild; Kumlien, Eva; Zelano, Johan
The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005-2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45-3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.
Reddy, Doodipala Samba
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
Background: Epilepsy is a disorder that is commonly found in people with intellectual disability (ID). The prevalence of epilepsy increases with the severity of ID. The objective of this study was to determine if there is an association between intelligence quotient (IQ) and epilepsy in children with ID. Materials and Methods: A total of 262 children, aged 3-18 years, with ID were identified as part of a community-based rehabilitation project. These children were examined for epilepsy and diagnosed by a psychiatrist and physicians based on results of electroencephalogram tests. A Spearman's correlation (ρ) was used to determine if there was an association between IQ scores and the occurrence of epilepsy. X2 statistics used to examine the relationship of epilepsy with gender, socioeconomic status, population type, severity of ID, family history of mental illness, mental retardation, epilepsy, and coexisting disorder. Results: Spearman's rho –0.605 demonstrates inverse association of IQ with epilepsy. X2 demonstrates statistically significant association (P < 0.05) with gender, severity of ID, cerebral palsy, behavior problems, and family history of mental illness, mental retardation, and epilepsy. Conclusions: Lower IQ score in children with ID has association with occurrence of epilepsy. Epilepsy is also found highly associated with male gender and lower age. PMID:24347947
Golding, Paul S.; Maddocks, L.; King, Terence A.; Drucker, D. B.
We demonstrate the killing of the oral bacteria Prevotella nigrescens using a photosensitizer and light from a 10 Hz, frequency doubled, Q-switched Nd:YAG pumped dye laser, with modified oscillator to increase output power. This system produced light at wavelengths close to 620 nm, the absorption maximum of the photosensitizing agent, malachite green isothiocyanate, a wavelength that is not significantly absorbed by tissue. A bacterial reduction of 97.5 percent was achieved at an energy density of 0.67 J/cm2 and exposure times of 300 seconds.
Ezeala-Adikaibe, B A; Achor, J U; Onwukwe, Jojo; Ekenze, O S; Onwuekwe, I O; Chukwu, O; Onyia, H; Ihekwaba, M; Obu, C
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
Alexopoulos, Andreas V.; Busch, Robyn M.; Wehner, Tim; Nair, Dileep; Bingaman, William E.; Najm, Imad M.
Objective: Misleading manifestations of common epilepsy syndromes might account for some epilepsy surgery failures, thus we sought to characterize patients with difficult to diagnose (atypical) mesial temporal lobe epilepsy (mTLE). Methods: We retrospectively reviewed our surgical database over 12 years to identify patients who underwent a standard anterior temporal lobectomy after undergoing intracranial EEG (ICEEG) evaluation with a combination of depth and subdural electrodes. We carefully studied electroclinical manifestations, neuroimaging data, neuropsychological findings, and indications for ICEEG. Results: Of 835 patients who underwent anterior temporal lobectomy, 55 were investigated with ICEEG. Ten of these had atypical mTLE features and were not considered to have mTLE preoperatively. All of them had Engel class I outcome for 3 to 7 years (median 3.85). Five reported uncommon auras, and 3 had no auras. Scalp-EEG and nuclear imaging studies failed to provide adequate localization. None had MRI evidence of hippocampal sclerosis. However, ICEEG demonstrated exclusive mesial temporal seizure onset in all patients. Clues suggesting the possibility of mTLE were typical auras when present, anterior temporal epileptiform discharges or ictal patterns, small hippocampi, asymmetrical or ipsilateral temporal hypometabolism on PET, anterior temporal hyperperfusion on ictal SPECT, and asymmetry of memory scores. Histopathology revealed hippocampal sclerosis in 6 patients and gliosis in 2. Conclusions: Atypical electroclinical presentation may be deceptive in some patients with mTLE. We emphasize the importance of searching for typical mTLE features to guide ICEEG study of mesial temporal structures in such patients, who may otherwise mistakenly undergo extramesial temporal resections or be denied surgery. PMID:24174582
Lytton, William W.
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
Lytton, William W
Epilepsy is a complex set of disorders that can involve many areas of the cortex, as well as underlying deep-brain systems. The myriad manifestations of seizures, which can be as varied as déjà vu and olfactory hallucination, can therefore give researchers insights into regional functions and relations. Epilepsy is also complex genetically and pathophysiologically: it involves microscopic (on the scale of ion channels and synaptic proteins), macroscopic (on the scale of brain trauma and rewiring) and intermediate changes in a complex interplay of causality. It has long been recognized that computer modelling 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 in modelling 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 the disorder.
Bercovici, Eduard; Kumar, Balagobal Santosh; Mirsattari, Seyed M.
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
Aoki, Ryo; Ito, Hiroshi
It has been reported that patients with epilepsy often have insomnia and/or daytime sleepiness; the symptomatologic features differ in seizure types. Not only the administration of anti-epileptics, but also inappropriate sleep hygiene cause daytime sleepiness. In subjective assessment of sleepiness, we need to pay attention if it can correctly assess or not. The prevalence of obstructive sleep apnea in patients with epilepsy is approximately 10-30%. Sleep apnea deteriorates the seizure control because of worsen sleep condition by sleep apnea, especially in elderly patients. Some researchers report that continuous positive airway pressure was effective for seizure control. Patients with epilepsy occasionally have REM sleep behavior disorder as comorbidity. Examination using polysomnography is required for differential diagnosis.
Rosenberg, Evan C; Tsien, Richard W; Whalley, Benjamin J; Devinsky, Orrin
Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.
Pandey, Swati; Singhi, Pratibha; Bharti, Bhavneet
Epilepsy is one of the most common neurological disorders prevalent in childhood period. There is scarcity of epidemiological data, required to plan services in resource constrained developing nations. To study the prevalence and treatment gap in childhood epilepsy in north Indian city, in the age group of 1-18 years. A two stage stratified cluster sampling; probability proportionate to size (PPS) was employed. A ten question screening questionnaire was employed to identify the presence of epilepsy. Definitions provided by International League against Epilepsy (ILAE) were used to classify screen positive subjects as epilepsy and to calculate the treatment gap. The prevalence rate for epilepsy was 6.24/1000 population. Febrile seizures and neurocysticercosis were most common causes of symptomatic seizures in childhood. This study of epidemiology of epilepsy provides valuable aid in optimizing effective community approach, thereby improving outcomes of childhood epilepsy.
Despite the introduction of at least 20 new antiepileptic drugs (AEDs) into clinical practice over the past decades, about one third of all epilepsies remain refractory to conventional forms of treatment. In addition, currently used AEDs have been developed to suppress neuronal hyperexcitability, but not necessarily to address pathogenic mechanisms involved in epilepsy development or progression (epileptogenesis). For those reasons endogenous seizure control mechanisms of the brain may provide alternative therapeutic opportunities. Adenosine is a well characterized endogenous anticonvulsant and seizure terminator of the brain. Several lines of evidence suggest that endogenous adenosine-mediated seizure control mechanisms fail in chronic epilepsy, whereas therapeutic adenosine augmentation effectively prevents epileptic seizures, even those that are refractory to conventional AEDs. New findings demonstrate that dysregulation of adenosinergic mechanisms are intricately involved in the development of epilepsy and its comorbidities, whereas adenosine-associated epigenetic mechanisms may play a role in epileptogenesis. The first goal of this review is to discuss how maladaptive changes of adenosinergic mechanisms contribute to the expression of seizures (ictogenesis) and the development of epilepsy (epileptogenesis) by focusing on pharmacological (adenosine receptor dependent) and biochemical (adenosine receptor independent) mechanisms as well as on enzymatic and transport based mechanisms that control the availability (homeostasis) of adenosine. The second goal of this review is to highlight innovative adenosine-based opportunities for therapeutic intervention aimed at reconstructing normal adenosine function and signaling for improved seizure control in chronic epilepsy. New findings suggest that transient adenosine augmentation can have lasting epigenetic effects with disease modifying and antiepileptogenic outcome. This article is part of the Special Issue entitled
Takahashi, Haruka; Hamada, Risa; Ogawa, Emiyu; Arai, Tsunenori
To study a mechanism of phrenic nerve preservation phenomena during a photosensitization reaction, we investigated an uptake of talaporfin sodium and photosensitization reaction effect on an electric propagation. Right phrenic nerve was completely preserved after superior vena cava isolations using the photosensitization reaction in canine animal experiments, in spite of adjacent myocardium was electrically blocked. We predicted that low drug uptake and/or low photosensitization reaction effect on the nerve might be a mechanism of that phenomena. To investigate uptake to various nerve tissue, a healthy extracted crayfish ventral nerve cord and an extracted porcine phrenic nerve were immersed in 20 μg/ml talaporfin sodium solution for 0-240 min. The mean talaporfin sodium fluorescence brightness increased depending on the immersion time. This brightness saturated around the immersion time of 120 min. We found that talaporfin sodium uptake inside the perineurium which directly related to the electric propagation function was lower than that of outside in the porcine phrenic nerve. To investigate photosensitization reaction effect on electric propagation, the crayfish nerve was immersed into the same solution for 15 min and irradiated by a 663 nm laser light with 120 mW/cm2. Since we found the action potential disappeared when the irradiation time was 25-65 s, we consider that the crayfish nerve does not tolerant to the photosensitization reaction on electric propagation function at atmospheric pressure. From these results, we think that the low uptake of talaporfin sodium inside the perineurium and low oxygen partial pressure of nerve might be the possible mechanism to preserve phrenic nerve in vivo.
Day, S M; Wu, Y W; Strauss, D J; Shavelle, R M; Reynolds, R J
To determine the causes of death of individuals with developmental disabilities that occur more frequently among those with remote symptomatic epilepsy (i.e., epilepsy occurring in persons with developmental delay or identified brain lesions) than for those without. The authors compared causes of mortality in persons with (n = 10,030) and without (n = 96,163) history of epilepsy in a California population of persons with mild developmental disabilities, 1988 to 2002. Subjects had traumatic brain injury, cerebral palsy, Down syndrome, autism, or a developmental disability with other or unknown etiology. There were 721,759 person-years of data, with 2,397 deaths. Underlying causes of death were determined from the State of California's official mortality records. Cause-specific death rates and standardized mortality ratios (SMRs) were computed for those with and without epilepsy relative to subjects in the California general population. Comparisons were then made between SMRs of those with and without epilepsy, and CIs on the ratios of SMRs were determined. Death rates for persons with epilepsy were elevated for several causes. The greatest excess was due to seizures (International Classification of Diseases-9 [ICD-9] 345; SMR 53.1, 95% CI 28.0 to 101.0) and convulsions (ICD-9 780.3; SMR 25.2, 95% CI 11.7 to 54.2). Other causes occurring more frequently in those with epilepsy included brain cancer (SMR 5.2, 95% CI 2.2 to 12.1), respiratory diseases (SMR 1.7, 95% CI 1.2 to 2.5), circulatory diseases (SMR 1.3, 95% CI 1.0 to 1.7), and accidents (SMR 2.7, 95% CI 1.9 to 3.7), especially accidental drowning (SMR 12.8, 95% CI 7.0 to 23.2). Remote symptomatic epilepsy is associated with an increased risk of death. Seizures, aspiration pneumonia, and accidental drowning are among the leading contributors.
Chow, Yun Sang
Phthalocyanines are versatile functional dyes that have shown great potential in cancer theranostics, especially in photodynamic therapy (PDT). This research work aims to develop "smart" phthalocyanine-based photosensitizers for targeted PDT. This thesis describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of several series of carefully designed phthalocyanine-based photosensitizers. Chapter 1 presents an overview of PDT, including its historical development, photophysical mechanisms, and biological mechanisms. Various classes of photosensitizers are introduced with emphasis putting on phthalocyanines, which exhibit ideal characteristics of photosensitizers for PDT. In recent years, several approaches have been used to develop photosensitizers with higher tumor selectivity and minimal skin photosensitivity after PDT. Activatable photosensitizers can provide a "turn on" mechanism to offer an additional control of the specificity of treatment. Photosensitizers can also work cooperatively with the tumor-targeting groups or anticancer drugs so as to achieve targeted or dual therapy, which can enhance the efficacy of PDT. The novel approaches mentioned above have been widely used and combined to form multi-functional photosensitizing agents. These novel concepts and development of PDT are discussed and illustrated with relevant examples at the end of this chapter. To minimize the prolonged skin photosensitivity, photosensitizers that can only be activated by tumor-associated stimuli have been developed. Due to the abnormal metabolism in tumor tissues, their surface usually exhibits a lower pH compared to that of the normal tissues. Also, the pH difference between the intracellular and the physiological environment provides a pH-activation mechanism. Chapter 2 presents the synthesis and spectroscopic characterization of a pH-responsive zinc(II) phthalocyanine tetramer, in which the phthalocyanine units
Sirven, Joseph I.
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
Patterson, Edward E
The mainstay of comparative research for epilepsy has been rodent models of induced epilepsy. This rodent basic science is essential, but it does not always translate to similar results in people, likely because induced epilepsy is not always similar enough to naturally occurring epilepsy. A good large animal, intermediate model would be very helpful to potentially bridge this translational gap. Epilepsy is the most common medical neurologic disease of dogs. It has been proposed since the 1970s that dogs with naturally occurring epilepsy could potentially be used as a comparative model for people of the underlying basis and therapy of epilepsy. There have been sporadic studies in the decades since then, with a relative surge in the last 10 years. These canine studies in the areas of genetics, drug therapy, dietary therapy, electroencelphalogram research, and devices for epilepsy show proof of concept that canine epilepsy can be a very good model for comparative research for many, but not all, facets of epilepsy. Results of research in canine epilepsy can and have benefited the improvement of treatment for both people and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Orsini, Alessandro; Zara, Federico; Striano, Pasquale
In last few years there has been rapid increase in the knowledge of epilepsy genetics. Nowadays, it is estimated that genetic epilepsies include over than 30% of all epilepsy syndromes. Several genetic tests are now available for diagnostic purposes in clinical practice. In particular, next-generation sequencing has proven to be effective in revealing gene mutations causing epilepsies in up to a third of the patients. This has lead also to functional studies that have given insight into disease pathophysiology and consequently to the identification of potential therapeutic targets opening the way of precision medicine for epilepsy patients. This minireview is focused on the most recent advances in genetics of epilepsies. We will also overview the modern genomic technologies and illustrate the diagnostic pathways in patients with genetic epilepsies. Finally, the potential implications for a personalized treatment (precision medicine) are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
Begley, Charles E; Durgin, Tracy L
To develop estimates of the direct cost of epilepsy in the United States for the general epilepsy population and sub-populations by systematically comparing similarities and differences in types of estimates and estimation methods from recently published studies. Papers published since 1995 were identified by systematic literature search. Information on types of estimates, study designs, data sources, types of epilepsy, and estimation methods was extracted from each study. Annual per person cost estimates from methodologically similar studies were identified, converted to 2013 U.S. dollars, and compared. From 4,104 publications discovered in the literature search, 21 were selected for review. Three were added that were published after the search. Eighteen were identified that reported estimates of average annual direct costs for the general epilepsy population in the United States. For general epilepsy populations (comprising all clinically defined subgroups), total direct healthcare costs per person ranged from $10,192 to $47,862 and epilepsy-specific costs ranged from $1,022 to $19,749. Four recent studies using claims data from large general populations yielded relatively similar epilepsy-specific annual cost estimates ranging from $8,412 to $11,354. Although more difficult to compare, studies examining direct cost differences for epilepsy sub-populations indicated a consistent pattern of markedly higher costs for those with uncontrolled or refractory epilepsy, and for those with comorbidities. This systematic review found that various approaches have been used to estimate the direct costs of epilepsy in the United States. However, recent studies using large claims databases and similar methods allow estimation of the direct cost burden of epilepsy for the general disease population, and show that it is greater for some patient subgroups. Additional research is needed to further understand the broader economic burden of epilepsy and how it varies across
Dustin, Irene; Resnick, Barbara; Galik, Elizabeth; Klinedinst, N Jennifer; Michael, Kathleen; Wiggs, Edythe
The purpose of this study was to test the psychometric properties of the revised Self-Efficacy for Exercise With Epilepsy (SEE-E) and Outcome Expectations for Exercise with Epilepsy (OEE-E) when used with people with epilepsy. The SEE-E and OEE-E were given in face-to-face interviews to 26 persons with epilepsy in an epilepsy clinic. There was some evidence of validity based on Rasch analysis INFIT and OUTFIT statistics. There was some evidence of reliability for the SEE-E and OEE-E based on person and item separation reliability indexes. These measures can be used to identify persons with epilepsy who have low self-efficacy and outcome expectations for exercise and guide design of interventions to strengthen these expectations and thereby improve exercise behavior.
Mathern, Gary W; Beninsig, Laurie; Nehlig, Astrid
From March 19 to June 30, 2014, Epilepsia conducted an open access online survey asking directed questions related to the 2014 Operational Definition of Epilepsy. This study reports the findings of that poll. The survey consisted of seven questions. Three questions addressed: (1) Criteria for when a person could be considered to have epilepsy after a single seizure; (2) if individuals with reflex seizures (unprovoked) have epilepsy; and (3) when epilepsy could be considered "resolved." Four added questions asked if responders were medical personal compared with patients and family members, geographic region of residence based on International League Against Epilepsy (ILAE) regions, and if responders had read the paper and if they were ILAE/International Bureau for Epilepsy (IBE) members. Of 476 that started the survey, 324 (68%) completed it. As recommended in the ILAE report, 43% agreed that if the chance of a second seizure after a first one was 61-90%, then a person could be considered to have epilepsy. More medical professionals agreed with the 61-90% criteria (55%) compared with patients (21%), while more patients indicated that epilepsy should only be defined after two unprovoked seizures (51%) compared with medical professionals (21%; p < 0.0001). The majority indicated that reflex seizures qualify a person as having epilepsy (79%). As recommended in the ILAE report, 51% agreed that the definition of a person with "resolved" epilepsy would be 10 years seizure-free and off medication for the last 5 years. More medical professionals agreed with this definition (59%) compared with patients (37%), while more patients indicated that epilepsy is never resolved (32%) compared with medical professionals (7%; p < 0.0001). There were no differences based on geographic residence. This survey found that the ILAE recommendations had the highest responses. However, there was clear disagreement with identified differences comparing medical personal with patients
Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C
We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.
Møller, Rikke S.; Heron, Sarah E.; Larsen, Line H. G.; Lim, Chiao Xin; Ricos, Michael G.; Bayly, Marta A.; van Kempen, Marjan J. A.; Klinkenberg, Sylvia; Andrews, Ian; Kelley, Kent; Ronen, Gabriel M.; Callen, David; McMahon, Jacinta M.; Yendle, Simone C.; Carvill, Gemma L.; Mefford, Heather C.; Nabbout, Rima; Poduri, Annapurna; Striano, Pasquale; Baglietto, Maria G.; Zara, Federico; Smith, Nicholas J.; Pridmore, Clair; Gardella, Elena; Nikanorova, Marina; Dahl, Hans Atli; Gellert, Pia; Scheffer, Ingrid E.; Gunning, Boudewijn; Kragh-Olsen, Bente; Dibbens, Leanne M.
Summary Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype–phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances. PMID:26122718
Sadler, R Mark; Rahey, Susan
A patient with a distinct aura of prescience as a manifestation of temporal lobe epilepsy was encountered. The experience prompted a review of this ictal phenomenon among patients attending a tertiary care epilepsy outpatient clinic. A computer epilepsy database was searched for patients with simple partial sensory seizures and complex partial seizures with auras. Identified patients had charts reviewed for details of the auras; patients were contacted and asked to provide written descriptions of their experiences. Literature searches (PubMed) were done by using the terms "precognition" or "prescience" and "seizures" or "epilepsy." Standard comprehensive epilepsy textbooks were reviewed. The charts of 218 patients were reviewed from 927 in the database; three had prescience as an ictal feature. The patients' descriptions were very similar in all cases (a profound sense of "knowing" what was going to happen in their environment in the immediate future). The experience was distinct from déjà vu and other psychic experiences. All patients probably have temporal lobe epilepsy. Only one other description of prescience as an ictal feature was found in the literature. Prescience can occur as an ictal feature of temporal lobe epilepsy and represents a previously underreported psychic phenomenon. The potential lateralizing value of this symptom is yet to be determined.
Krishnaiah, Balaji; Alwar, Seenivasan P.; Ranganathan, Lakshmi N.
Introduction: People living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions, and misunderstandings that have persisted for many years. In the last decade, there has been an increase in individual literacy rate and increased access to technology in rural population. However, it is unclear if this has any effect on knowledge, attitude, and practice (KAP) attitude toward epilepsy. Objective: Our primary aim is to evaluate KAP toward epilepsy. In addition, we also estimated the prevalence of stroke and epilepsy in rural South India. Materials and Methods: Using a 14-item questionnaire, we assessed KAP toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy and 10-item questionnaires to assess the prevalence of epilepsy and stroke among 500 randomly selected populations in a Pattaravakkam village (Tamil Nadu, India). Results: About 87.7% of the people had heard or read about epilepsy. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (23.1%), kind of insanity (22.6%), or as contagious (12.0%). The knowledge about the clinical characteristics and first aid to a person during a seizure was 25.8%. About 36.5% of people think that society discriminates people with epilepsy. Moreover, our prevalence study showed that 8.7% people are suffering from epilepsy and 3.7% had stroke previously and at the day of survey, the stroke prevalence is 3.3%. Conclusion: Even with increased literacy, technology, and communication devices, the KAP of people toward epilepsy is relatively low. General public education campaigns and specific school education campaigns children should be encouraged to increase the KAP toward epilepsy. The prevalence and pattern of epilepsy and stroke is on the higher side in the village of Pattaravakkam. Future research regarding the value of targeted education in improving KAP will be worthwhile. PMID:27365954
Krishnaiah, Balaji; Alwar, Seenivasan P; Ranganathan, Lakshmi N
People living with epilepsy continue to suffer from enacted or perceived stigma that is based on myths, misconceptions, and misunderstandings that have persisted for many years. In the last decade, there has been an increase in individual literacy rate and increased access to technology in rural population. However, it is unclear if this has any effect on knowledge, attitude, and practice (KAP) attitude toward epilepsy. Our primary aim is to evaluate KAP toward epilepsy. In addition, we also estimated the prevalence of stroke and epilepsy in rural South India. Using a 14-item questionnaire, we assessed KAP toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy and 10-item questionnaires to assess the prevalence of epilepsy and stroke among 500 randomly selected populations in a Pattaravakkam village (Tamil Nadu, India). About 87.7% of the people had heard or read about epilepsy. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (23.1%), kind of insanity (22.6%), or as contagious (12.0%). The knowledge about the clinical characteristics and first aid to a person during a seizure was 25.8%. About 36.5% of people think that society discriminates people with epilepsy. Moreover, our prevalence study showed that 8.7% people are suffering from epilepsy and 3.7% had stroke previously and at the day of survey, the stroke prevalence is 3.3%. Even with increased literacy, technology, and communication devices, the KAP of people toward epilepsy is relatively low. General public education campaigns and specific school education campaigns children should be encouraged to increase the KAP toward epilepsy. The prevalence and pattern of epilepsy and stroke is on the higher side in the village of Pattaravakkam. Future research regarding the value of targeted education in improving KAP will be worthwhile.
Giussani, Giorgia; Canelli, Valentina; Bianchi, Elisa; Franchi, Carlotta; Nobili, Alessandro; Erba, Giuseppe; Beghi, Ettore
Drug-resistant epilepsy (DRE) is defined by the International League Against Epilepsy as a failure of adequate trials of two tolerated, appropriately chosen, and used antiepileptic drugs to achieve sustained seizure freedom. Our aim was to calculate the following: (1) the prevalence of active epilepsy and DRE in a well-defined population of Northern Italy and (2) the proportion of incident cases developing DRE. The study population (146,506; year 2008) resided in the province of Lecco, Northern Italy. The medical records of 123 general practitioners were reviewed to identify patients with epilepsy, diagnosed by a neurologist during the period 2000-2008. The point prevalence of active epilepsy and DRE was calculated on December 31, 2008. A total of 747 prevalent patients with epilepsy, 684 patients with active epilepsy, and 342 incident cases were identified. The frequency of DRE was 15.6% (107/684) of all active epilepsies and 10.5% (36/342) of incident cases. The point prevalence was 0.73 per 1000. The standardized prevalence of DRE was 0.7 per 1000 (Italian population) and 0.8 per 1000 (world population). Our data indicate that 1/6 patients with active epilepsy in the general population has DRE, and 1/10 patients with newly diagnosed epilepsy will develop DRE within nine years from the diagnosis. Copyright © 2015 Elsevier Inc. All rights reserved.
Prabhakaran, Vasudevan; Drevets, Douglas A; Ramajayam, Govindan; Manoj, Josephine J; Anderson, Michael P; Hanas, Jay S; Rajshekhar, Vedantam; Oommen, Anna; Carabin, Hélène
Neurocysticercosis (NCC), a neglected tropical disease, inflicts substantial health and economic costs on people living in endemic areas such as India. Nevertheless, accurate diagnosis using brain imaging remains poorly accessible and too costly in endemic countries. The goal of this study was to test if blood monocyte gene expression could distinguish patients with NCC-associated epilepsy, from NCC-negative imaging lesion-free patients presenting with idiopathic epilepsy or idiopathic headaches. Patients aged 18 to 51 were recruited from the Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India, between January 2013 and October 2014. mRNA from CD14+ blood monocytes was isolated from 76 patients with NCC, 10 Recovered NCC (RNCC), 29 idiopathic epilepsy and 17 idiopathic headaches patients. A preliminary microarray analysis was performed on six NCC, six idiopathic epilepsy and four idiopathic headaches patients to identify genes differentially expressed in NCC-associated epilepsy compared with other groups. This analysis identified 1411 upregulated and 733 downregulated genes in patients with NCC compared to Idiopathic Epilepsy. Fifteen genes up-regulated in NCC patients compared with other groups were selected based on possible relevance to NCC, and analyzed by qPCR in all patients' samples. Differential gene expression among patients was assessed using linear regression models. qPCR analysis of 15 selected genes showed generally higher gene expression among NCC patients, followed by RNCC, idiopathic headaches and Idiopathic Epilepsy. Gene expression was also generally higher among NCC patients with single cyst granulomas, followed by mixed lesions and single calcifications. Expression of certain genes in blood monocytes can distinguish patients with NCC-related epilepsy from patients with active Idiopathic Epilepsy and idiopathic headaches. These findings are significant because they may lead to the development of new tools to
Carreño, Mar; Bien, Christian G; Asadi-Pooya, Ali A; Sperling, Michael; Marusic, Petr; Elisak, Martin; Pimentel, Jose; Wehner, Tim; Mohanraj, Rajiv; Uranga, Juan; Gómez-Ibáñez, Asier; Villanueva, Vicente; Gil, Francisco; Donaire, Antonio; Bargalló, Nuria; Rumià, Jordi; Roldán, Pedro; Setoain, Xavier; Pintor, Luis; Boget, Teresa; Bailles, Eva; Falip, Mercè; Aparicio, Javier; Dalmau, Josep; Graus, Francesc
We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Carreño, Mar; Bien, Christian; Asadi-Pooya, Ali A.; Sperling, Michael; Marusic, Petr.; Elisak, Martin; Pimentel, Jose; Wehner, Tim; Mohanraj, Rajiv; Uranga, Juan; Gómez-Ibáñez, Asier; Villanueva, Vicente; Gil, Francisco; Donaire, Antonio; Bargalló, Nuria; Rumià, Jordi; Roldán, Pedro; Setoain, Xavier; Pintor, Luis; Boget, Teresa; Bailles, Eva; Falip, Mercè; Aparicio, Javier; Dalmau, Josep; Graus, Francesc
We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel`s classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients. PMID:28043058
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
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.
Toxqui-López, S.; Hernández-Hernández, E.; Santacruz-Vázquez, C.; Olivares-Pérez, A.; Santacruz-Vazquez, V.
One of the natural most employed within the food industry are pigments of betalains by their solubility in water to give desired colorations in processed foods such as beverages, dairy, meat. However, this research shows that this type of pigments can be used as photosensitizing agents in the field of holographic recording materials.
Hussain, Saimah; Harris, Frederick; Phoenix, David A
The ability of phenothiazinium-based photosensitizers to induce photodamage to Escherichia coli membranes is investigated. Phenothiazinium-based photosensitizers were found to be somewhat lipophilic (log P>0.7) and to induce surface-pressure changes (3-12 mN m(-1)) in lipid monolayers mimetic of bacterial membranes, implying that these molecules are able to penetrate biological membranes. Under dark and light conditions (3.15 J cm(-1) for 30 min), phenothiazinium-based photosensitizers were incubated with E. coli cells. These cells showed levels of dark bacteriolysis that ranged between 6% and 13%, with light conditions leading to no significant increase in these levels. Gas chromatography-based analyses showed such incubations to produce no significant changes in the levels of C(16) and C(18) fatty acid chain saturation found in E. coli whole lipid-extracts. It is concluded that the phenothiazinium-based photosensitizers studied may not use E. coli membranes as their primary photodynamic target, but may inflict photodamage on cytoplasmic targets, possibly DNA.
Peumans, Peter; Forrest, Stephen R.
Solid state photosensitive devices including photovoltaic devices are provided which comprise a first electrode and a second electrode in superposed relation; and at least one isolated Light Harvesting Complex (LHC) between the electrodes. Preferred photosensitive devices comprise an electron transport layer formed of a first photoconductive organic semiconductor material, adjacent to the LHC, disposed between the first electrode and the LHC; and a hole transport layer formed of a second photoconductive organic semiconductor material, adjacent to the LHC, disposed between the second electrode and the LHC. Solid state photosensitive devices of the present invention may comprise at least one additional layer of photoconductive organic semiconductor material disposed between the first electrode and the electron transport layer; and at least one additional layer of photoconductive organic semiconductor material, disposed between the second electrode and the hole transport layer. Methods of generating photocurrent are provided which comprise exposing a photovoltaic device of the present invention to light. Electronic devices are provided which comprise a solid state photosensitive device of the present invention.
Dillon, J. N.
Photosensitive filler is added to curable epoxy resins to minimize stress from internal shrinkage during curing or polymerization. Cinnamic acid resins and cinnamal ketones may be added in the amount of 1 to 3 percent by weight of the resin mixture.
Burchinov, A. N.; Kiselev, V. M.; Penni, A. A.; Khistyaeva, V. V.
The photosensitized generation of singlet oxygen in solutions of rhenium(I) complex fac-[Re(bipy)(CO)3NCCH3]+OTf-, where bipy=2,2'-bipyridine, in chloride methylene and carbon tetrachloride under continuous LED irradiation in the UV and visible ranges has been investigated.
Acquired disease resistance of plants may be induced by exogenous reactive oxygen species or their sources. Certain compounds (photosensitizers) produce ROS at the expense of light energy. This study used photodynamic dyes bengal rose and methylene blue, which yield singlet oxygen, and mercaptopyrid...
Li, Bu-hong; Xie, Shu-sen; Lu, Zu-kang
The spectral properties of new photosensitizer ZnPcS2P2, PsD-007 and HMME, as well as traditional photosensitizer HpD have been studied by comparing their spectra in physiological saline and in physiological saline with 10 percent serum. Experimental results show that the maximum absorption peaks for PsD-007, HMME and HpD in the physiological saline with 10 percent serum appear at 400 nm in the soret region, while at 670 nm for ZnPcS2P2. The fluorescence excitation spectra closely resemble the absorption spectra. When excited by the light at the wavelengths of 413 and 514.5 nm, the fluorescence emission peaks for PsD-007, HMME and HpD appear at 625 and 690 nm, respectively. The fluorescent excitation efficiency of the same photosensitizer with the same concentration excited by the light at the wavelength of 413 nm is about three fold higher than that at 514.5 nm. Furthermore, the fluorescent excitation efficiency is the highest for HMME, but is lower for HpD and lowest for PsD-007. These results are significant in the selection of photosensitizers for photodynamic diagnosis and therapy.
Thompson, Mark E [Anaheim Hills, CA; Li, Jian [Los Angeles, CA; Forrest, Stephen [Princeton, NJ; Rand, Barry [Princeton, NJ
An organic photosensitive optoelectronic device, having an anode, a cathode, and an organic blocking layer between the anode and the cathode is described, wherein the blocking layer comprises a phenanthroline derivative, and at least partially blocks at least one of excitons, electrons, and holes.
Machado, Neila; Carvalho, B. G.; Téllez Soto, C. A.; Martin, A. A.; Favero, P. P.
Photodynamic therapy is an alternative form of cancer treatment that meets the desire for a less aggressive approach to the body. It is based on the interaction between a photosensitizer, activating light, and molecular oxygen. This interaction results in a cascade of reactions that leads to localized cell death. Many studies have been conducted to discover an ideal photosensitizer, which aggregates all the desirable characteristics of a potent cell killer and generates minimal side effects. Using Density Functional Theory (DFT) implemented in the program Vienna Ab-initio Simulation Package, new chlorin derivatives with different functional groups were simulated to evaluate the different absorption wavelengths to permit resonant absorption with the incident laser. Gaussian 09 program was used to determine vibrational wave numbers and Natural Bond Orbitals. The chosen drug with the best characteristics for the photosensitizer was a modified model of the original chlorin, which was called as Thiol chlorin. According to our calculations it is stable and is 19.6% more efficient at optical absorption in 708 nm in comparison to the conventional chlorin e6. Vibrational modes, optical and electronic properties were predicted. In conclusion, this study is an attempt to improve the development of new photosensitizer drugs through computational methods that save time and contribute to decrease the numbers of animals for model application.
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
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.
Epilepsy and migraine are chronic neurological disorders with episodic manifestations that are commonly treated in neurological practice and frequently occur together. In this review we examine similarities and contrasts between these disorders, with focus on epidemiology and classification, temporal coincidence, triggers, and mechanistically based therapeutic overlap. This investigation draws attention to unique aspects of both epilepsy and migraine, while identifying areas of crossover in which each specialty could benefit from the experience of the other. PMID:16426991
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
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.
Friedman, Daniel; Fahlstrom, Robyn
Little is known about the ethnic and racial differences in the prevalence of generalized and focal epilepsy among patients with non-acquired epilepsies. In this study, we examined epilepsy classification and race/ethnicity in 813 probands from sibling or parent-child pairs with epilepsy enrolled in the Epilepsy Genome/Phenome Project (EPGP). Subjects were classified as generalized epilepsy (GE), non-acquired focal epilepsy (NAFE), mixed epilepsy syndrome (both generalized and focal), and unclassifiable, based on consensus review of semiology and available clinical, electrophysiology, and neuroimaging data. In this cohort, 628 (77.2%) subjects identified exclusively as Caucasian/white and 65 (8.0%) subjects reported African ancestry, including subjects of mixed-race. Of the Caucasian/white subjects, 357 (56.8%) had GE, 207 (33.0%) had NAFE, 32 (5.1%) had a mixed syndrome, and 32 (5.1%) were unclassifiable. Among subjects of African ancestry, 28 (43.1%) had GE, 27 (41.5%) had NAFE, 2 (3.1%) had a mixed syndrome, and 8 (12.3%) were unclassifiable. There was a higher proportion of subjects with GE compared to other syndromes among Caucasians/whites compared to subjects with African ancestry (OR 1.74, 95% CI: 1.04-2.92, two-tailed Fisher's exact test, p=0.036). There was no difference in the rate of GE among subjects reporting Hispanic ethnicity (7.6% of total) when adjusted for race (Caucasian/white vs non-Caucasian/white; OR 0.65, 95% CI: 0.40-1.06, p>0.05). The proportion of participants with unclassifiable epilepsy was significantly greater in those of African-American descent. In a group of patients with epilepsy of unknown etiology and an affected first degree relative, GE is more common among Caucasian/white subjects than among those with African ancestry. These findings suggest there may be geographical differences in the distribution of epilepsy susceptibility genes and an effect of genetic background on epilepsy phenotype. However, the results should be
Granados, Ana M; Orejuela, Juan F
Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897
Oh, Ahyuda; Thurman, David J; Kim, Hyunmi
Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤18years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI=122-129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI=58.1-61.0 vs. 23%, CI=23.1-23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI=34.3-37.1) than those without epilepsy (8%, 99% CI=7.45-7.51, P<0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI=26.9-29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR=29.8, 99% CI=23.7-37.3, P<0
Leach, J P; Smith, P E; Craig, J; Bagary, M; Cavanagh, D; Duncan, S; Kelso, A R C; Marson, A G; McCorry, D; Nashef, L; Nelson-Piercy, C; Northridge, R; Sieradzan, K; Thangaratinam, S; Walker, M; Winterbottom, J; Reuber, M
Between 2009 and 2012 there were 26 epilepsy-related deaths in the UK of women who were pregnant or in the first post-partum year. The number of pregnancy-related deaths in women with epilepsy (WWE) has been increasing. Expert assessment suggests that most epilepsy-related deaths in pregnancy were preventable and attributable to poor seizure control. While prevention of seizures during pregnancy is important, a balance must be struck between seizure control and the teratogenic potential of antiepileptic drugs (AEDs). A range of professional guidance on the management of epilepsy in pregnancy has previously been issued, but little attention has been paid to how optimal care can be delivered to WWE by a range of healthcare professionals. We summarise the findings of a multidisciplinary meeting with representation from a wide group of professional bodies. This focussed on the implementation of optimal pregnancy epilepsy care aiming to reduce mortality of epilepsy in mothers and reduce morbidity in babies exposed to AEDs in utero. We identify in particular -What stage to intervene - Golden Moments of opportunities for improving outcomes -Which Key Groups have a role in making change -When - 2020 vision of what these improvements aim to achieve. -How to monitor the success in this field We believe that the service improvement ideas developed for the UK may provide a template for similar initiatives in other countries. Copyright © 2017 British Epilepsy Association. All rights reserved.
Bennett, Louise; Bergin, Michael; Gooney, Martina; Doherty, Colin P; Synnott, Cara; Wells, John S G
A challenge facing modern health care systems is to develop and implement new models of service that deliver increased capacity while providing a higher-quality, more cost-effective service within resource constraints. Incorporating the experience of people with epilepsy must be seen as central to the effectiveness of service design and delivery. This paper, therefore, reports the views of people with epilepsy with regards to health service delivery in Ireland. A cross-sectional descriptive survey design involving both quantitative and qualitative items was administered to a convenience sample of one hundred and two people with epilepsy (n=102) attending an epilepsy specialist centre. Despite high levels of satisfaction with hospital and primary care, participants offered several suggestions to improve healthcare delivery, such as: less delay in accessing specialist care and hospital appointments; better communication; and easier access to investigatory services. Findings demonstrate that for people with epilepsy the burden of the disorder is substantial and complex encompassing social, psychological and structural difficulties. Poor information provision particularly among women is reported. Furthermore, a lack of empowerment in people with epilepsy is highlighted. This study has implications for the reform and development of epilepsy services in relation to practice, education and research. It provides a basis for an evaluation of current practice and identifies opportunities for future service reorganization to improve the quality and efficiency of healthcare provision. Copyright © 2015 Elsevier B.V. All rights reserved.
Sahoo, Satya S; Zhang, Guo-Qiang; Lhatoo, Samden D
The epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology-driven informatics infrastructure and its role in adoption of a "data-driven" paradigm in epilepsy research. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Thomas, Rhys H; Mullins, Jane M; Waddington, Tracey; Nugent, Kane; Smith, Phil E M
An epilepsy diagnosis is very verbal, relying on witness history, personal narrative and analysis of how people describe the experience. Occasionally however, non-verbal descriptions of seizures allow us to gain a fuller understanding of this complex disorder. Artists are often inspired by personal experience, so it should be no surprise to find people depicting images of ill health, both their own and people they have observed. Furthermore, an ailment or affliction may influence an artist's portfolio over their lifetime, such as de Kooning's Alzheimer's disease and Monet's glaucoma. Epilepsy (in contrast with cerebrovascular or neurodegenerative disease) may present not just with a loss of function but with unusual super-added experiences such as déjà vu, ecstatic auras or hallucinations. Here we describe some artists who were thought to have had epilepsy, and the way in which their seizures influenced their art. It appears that for some, they have succeeded despite, rather than because of, their epilepsy and that rather than be inspired by their symptoms they were ashamed of them. If there is a common theme, it is in the unwanted psychological harm of some seizures provoking dark, frustrated imagery.
ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.
Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360
Verrotti, Alberto; Cerminara, Caterina; Domizio, Sergio; Mohn, Angelika; Franzoni, Emilio; Coppola, Giangennaro; Zamponi, Nelia; Parisi, Pasquale; Iannetti, Paola; Curatolo, Paolo
The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrolment into…
Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone-related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Marks, Warren A; Hernandez, Angel; Gabriel, Marsha
Rehabilitation represents not only a distinct field of medicine, but also a philosophical and practical treatment approach that can be applied to a variety of chronic disorders. Neurology encompasses many chronic disorders, making it ideal for the application of rehabilitation principles in daily practice. Epilepsy offers a unique opportunity to incorporate rehabilitation principles into the management of a complex medical disorder. Epilepsy is an evolving disease process that changes with the maturation of the central nervous system. The rehabilitative model provides the framework for a dynamic treatment plan to meet the changing needs of the child with epilepsy through the social and developmental changes of childhood, adolescence, and adulthood. The development of epilepsy may complicate the recovery from many acute and chronic conditions that affect the central nervous system. The rehabilitation process must address these many aspects of the disease process and its sequelae. This makes neurologists uniquely qualified to manage the rehabilitation team. The impact of the therapeutic milieu on the recovery process may be as important as any specific medical or surgical intervention.
Tanaka, Akihiro; Akamatsu, Naoki; Shouzaki, Taisaku; Toyota, Tomoko; Yamano, Mitsuhiko; Nakagawa, Masanori; Tsuji, Sadatoshi
Epidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. We searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. We identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. The most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Chen, Tian; Giri, Mohan; Xia, Zhenyi; Subedi, Yadu Nanda; Li, Yan
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
Ramaratnam, S; Baker, G A; Goldstein, L H
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), and MEDLINE (1966 to March 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety
Ramaratnam, Sridharan; Baker, Gus A; Goldstein, Laura H
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group's Specialized Register (1 July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to March 2007). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy. Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life. We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. Two trials found cognitive behavioural therapy (CBT) to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. Two trials of CBT found improvement in quality of life scores. One trial of group cognitive therapy found no significant effect on seizure frequency while another trial found statistically significant reduction in seizure frequency as well as in seizure index (product of seizure frequency and seizure duration in seconds) among subjects treated with CBT. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions
Kolahi, Ali-Asghar; Abbasi-Kangevari, Mohsen; Bakhshaei, Pouya; Mahvelati-Shamsabadi, Farhad; Tonekaboni, Seyed-Hassan; Farsar, Ahmad-Reza
Knowledge about epilepsy and attitudes towards patients with epilepsy can affect measures taken to manage epilepsy and seizures. Support and understanding of mothers is invaluable in enabling children with epilepsy to develop normal life skills in living with epilepsy. In order to identify the educational needs of mothers of children with epilepsy, their knowledge, attitudes, and practices should be assessed. Therefore, we interviewed a group of mothers of children with epilepsy who were referred to a pediatric neurology clinic in a teaching hospital. The objective of this study was to assess knowledge, attitudes, and practices among mothers of children with epilepsy in order to identify their educational needs. In the period of August 2014 to January 2015, mothers whose children were diagnosed with epilepsy for at least six months participated in this cross sectional study, while returning to the neurology clinic of a pediatric hospital for usual follow-up. Data were collected through face-to-face interviews, held by trained female general practitioners. The interviewer used questions from a questionnaire. The knowledge section of the questionnaire included questions regarding prevalence and general knowledge about epilepsy, its etiology, symptoms, and seizure provoking factors. The attitudes section included statements regarding the mother's attitudes towards epilepsy and patients with the disease. The practice section included questions about first-aid measures taken by mothers who had witnessed generalized seizures by the time of interview. Responses of 206 participants were analyzed. At least 83% of mothers knew that epilepsy is a noncontagious neurological disorder which can be treated by regular drug therapy. In spite of demonstrating good knowledge scores, the majority of mothers felt the need for further training in epilepsy. More than 98% of mothers were against the idea that patients with epilepsy should hide their disease. Though having been referred to
Ramsey, Rachelle R; Loiselle, Kristin; Rausch, Joseph R; Harrison, Jordan; Modi, Avani C
The objective of this study was 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. 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 postdiagnosis. 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 were collected via MEMS TrackCaps, and medical information was collected through chart review. 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. The number of AEDs, internalizing problems, and externalizing problems emerged as the most consistent predictors across the HRQOL domains. 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. Copyright © 2016 Elsevier Inc. All rights reserved.
Ramsey, Rachelle R.; Loiselle, Kristin; Rausch, Joseph R.; Harrison, Jordan; Modi, Avani C.
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
Jia, Peilin; Ewers, Jeffrey M.; Zhao, Zhongming
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
Jia, Peilin; Ewers, Jeffrey M; Zhao, Zhongming
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
Rosenberg, Evan C; Patra, Pabitra H; Whalley, Benjamin J
cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ 9 -THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy. This article is part of a Special Issue titled Cannabinoids and Epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.
Meyer, Ana-Claire L.; Dua, Tarun; Boscardin, John; Escarce, José J.; Saxena, Shekhar; Birbeck, Gretchen L.
Purpose Epilepsy is one of the most common serious neurological disorders worldwide. Our objective was to determine which economic, healthcare, neurology and epilepsy specific resources were associated with untreated epilepsy in resource-constrained settings. Methods A systematic review of the literature identified community-based studies in resource-constrained settings that calculated the epilepsy treatment gap, the proportion with untreated epilepsy, from prevalent active epilepsy cases. Economic, healthcare, neurology and epilepsy specific resources were taken from existing datasets. Poisson regression models with jackknifed standard errors were used to create bivariate and multivariate models comparing the association between treatment status and economic and health resource indicators. Relative risks were reported. Key Findings Forty-seven studies of 8285 individuals from 24 countries met inclusion criteria. Bivariate analysis demonstrated that individuals residing in rural locations had significantly higher risks of untreated epilepsy [Relative Risk(RR)=1.63; 95% confidence interval(CI):1.26,2.11]. Significantly lower risks of untreated epilepsy were observed for higher physician density [RR=0.65, 95% CI:0.55,0.78], presence of a lay [RR=0.74, 95%CI:0.60,0.91] or professional association for epilepsy [RR=0.73, 95%CI:0.59,0.91], or post-graduate neurology training program [RR=0.67, 95%CI:0.55, 0.82]. In multivariate models, higher physician density maintained significant effects [RR=0.67; 95%CI:0.52,0.88]. Significance Even among resource-limited regions, people with epilepsy in countries with fewer economic, healthcare, neurology and epilepsy specific resources are more likely to have untreated epilepsy. Community-based epilepsy care programs have improved access to treatment but in order to decrease the epilepsy treatment gap, poverty and inequalities of healthcare, neurological and epilepsy resources must be dealt with at the local, national, and global
Brooks-Kayal, Amy R.; Bath, Kevin G.; Berg, Anne T.; Galanopoulou, Aristea S.; Holmes, Gregory L.; Jensen, Frances E.; Kanner, Andres M.; O’Brien, Terence J.; Whittemore, Vicky H.; Winawer, Melodie R.; Patel, Manisha; Scharfman, Helen E.
Summary Many symptoms of neurologic or psychiatric illness—such as cognitive impairment, depression, anxiety, attention deficits, and migraine—occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure. PMID:23909853
Sha'ari, Hidayati Mohd; Haerian, Batoul Sadat; Baum, Larry; Tan, Hui Jan; Rafia, Mohd Hanip; Kwan, Patrick; Cherny, Stacey S; Sham, Pak Chung; Gui, Hongsheng; Raymond, Azman Ali; Lim, Kheng Seang; Mohamed, Zahurin
Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese.
de Ávila, Renato Ivan; Teixeira, Gabriel Campos; Veloso, Danillo Fabrini Maciel Costa; Moreira, Larissa Cleres; Lima, Eliana Martins; Valadares, Marize Campos
This study evaluated the applicability of a modified Direct Peptide Reactivity Assay (DPRA) (OECD N° 442C, 2015) through the 10-fold reduction of reaction volume (micro-DPRA, mDPRA) for skin sensitization evaluation of six commercial glyphosate-containing formulations. In addition, another modification of DPRA was proposed by adding a UVA (5J/cm 2 ) irradiation step, namely photo-mDPRA, to better characterize (photo)sensitizer materials. The phototoxicity profile of pesticides was also evaluated using the 3T3 Neutral Red Uptake Phototoxicity Test (3T3-NRU-PT) (OECD N° 432, 2004). The mDPRA could represent an environmentally acceptable test approach, since it reduces costs and organic waste. Peptide depletion was greater in photo-mDPRA and changed the reactivity class of each test material, in comparison to mDPRA. Thus, the association of mDPRA with photo-mDPRA was better for correctly characterizing human (photo)sensitizer substances and pesticides. In general, cysteine depletion was greater than that of lysine for all materials tested in both mDPRA and photo-mDPRA. Furthermore, while 3T3-NRU-PT is unable to predict (photo)sensitizers, it was capable of correctly identifying the phototoxic potential of the tested agrochemical formulations. In conclusion, mDPRA plus photo-mDPRA and 3T3-NRU-PT seem to be preliminary non-animal test batteries for skin (photo)sensitization/phototoxicity assessment of chemicals, agrochemical formulations and their ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.
Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo
The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554
Lilleker, James B; Jones, Matthew S; Mohanraj, Rajiv
In a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. We reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. We identified 6 (4.2%) patients who had titres of >400 pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. Patients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Ngoungou, Edgard B; Bhalla, Devender; Nzoghe, Amandine; Dardé, Marie-Laure; Preux, Pierre-Marie
Toxoplasmosis is an important, widespread, parasitic infection caused by Toxoplasma gondii. The chronic infection in immunocompetent patients, usually considered as asymptomatic, is now suspected to be a risk factor for various neurological disorders, including epilepsy. We aimed to conduct a systematic review and meta-analysis of the available literature to estimate the risk of epilepsy due to toxoplasmosis. A systematic literature search was conducted of several databases and journals to identify studies published in English or French, without date restriction, which looked at toxoplasmosis (as exposure) and epilepsy (as disease) and met certain other inclusion criteria. The search was based on keywords and suitable combinations in English and French. Fixed and random effects models were used to determine odds ratios, and statistical significance was set at 5.0%. Six studies were identified, with an estimated total of 2888 subjects, of whom 1280 had epilepsy (477 positive for toxoplasmosis) and 1608 did not (503 positive for toxoplasmosis). The common odds ratio (calculated) by random effects model was 2.25 (95% CI 1.27-3.9), p = 0.005. Despite the limited number of studies, and a lack of high-quality data, toxoplasmosis should continue to be regarded as an epilepsy risk factor. More and better studies are needed to determine the real impact of this parasite on the occurrence of epilepsy.
Garcia, John; Wical, Beverly; Wical, William; Schaffer, Leah; Wical, Thomas; Wendorf, Heather; Roiko, Samuel
To examine the risk of obstructive sleep apnea (OSA) in children with cerebral palsy (CP) and/or epilepsy. This cross-sectional study employs the Pediatric Sleep Questionnaire (PSQ), the Gross Motor Function Classification System (GMFCS), and chart review to identify symptoms of OSA in children presenting to a multi-specialty pediatric healthcare institution. Two-hundred and fifteen patients were grouped into those with epilepsy (n=54), CP (n=18), both (n=55), and neither (comparison group, n=88). The comparison group comprised children with developmental disabilities but not children with typical development. Significantly increased PSQ scores (indicating increased risk of OSA) were found among children with CP (58%) and CP with epilepsy (67%) than among the comparison group (27%; p<0.001 and p<0.0001 respectively). Children with both CP and epilepsy had a greater number of increased PSQ scores compared with CP alone (p<0.05). Increased PSQ scores were observed with increasing CP severity as measured using the GMFCS. The PSQ identified more children at risk of OSA (46%) than did the medical record review for symptoms of OSA (8.2%, p<0.001). Children with CP of greater severity or comorbid epilepsy are at increased risk of OSA. This study supports the routine questionnaire-based assessment for OSA as a regular part of the care of all children with CP, especially in those with more severe CP and those with epilepsy. © 2016 Mac Keith Press.
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
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
Kettner, Laura O; Ramlau-Hansen, Cecilia H; Kesmodel, Ulrik S; Bay, Bjørn; Matthiesen, Niels B; Henriksen, Tine B
A few studies have indicated an increased risk of epilepsy in children conceived by fertility treatment possibly due to characteristics of the infertile couple rather than the treatment. We therefore aimed to investigate the association between parental infertility, fertility treatment, and epilepsy in the offspring, including the subtypes of epilepsy; idiopathic generalised epilepsy and focal epilepsy. This cohort included all pregnancies resulting in liveborn singletons from the Aarhus Birth Cohort, Denmark (1995-2013). Information on time to pregnancy and fertility treatment was obtained from pregnancy questionnaires in early pregnancy. Children developing epilepsy were identified from the Danish National Patient Register and the Danish National Prescription Registry until 2013. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. A total of 60 440 pregnancies were included, and 0.8% of the children developed epilepsy.The primary analyses showed no association between parental infertility or fertility treatment, and the overall risk of childhood epilepsy (hazard rate ratios (HRs); 95% confidence intervals (CIs): 1.08 (0.73, 1.60) and 1.04 (0.71, 1.52)). In secondary analyses, both parental infertility and fertility treatment were associated with an increased risk of idiopathic generalised epilepsy (HRs and 95% CIs: 2.25 (1.10, 4.58) and 2.45 (1.26, 4.75)). No association was seen for focal epilepsy. Parental infertility or fertility treatment was not associated with an overall risk of childhood epilepsy. Parental infertility may be associated with an increased risk of idiopathic generalised epilepsy; a subtype of epilepsy believed to be of genetic origin. © 2016 John Wiley & Sons Ltd.
Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M.; Thom, Maria; Harper, Ronald M.; Sander, Josemir W.; Vos, Sjoerd B.; Duncan, John S.; Lhatoo, Samden
Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. PMID:26264515
Aregahegn, Kifle; Nozière, Barbara; George, Christian
Humankind is facing a changing environment possibly due to anthropogenic stress on the atmosphere. In this context, aerosols play a key role by affecting the radiative climate forcing, hydrological cycle, and by their adverse effect on health. The role of organic compounds in these processes is however still poorly understood because of their massive chemical complexity and numerous transformations. This is particularly true for Secondary Organic Aerosol (SOA), which are produced in the atmosphere by organic gases. Traditionally, the driving forces for SOA growth is believed to be the partitioning onto aerosol seeds of condensable gases, either emitted primarily or resulting from the gas phase oxidation of organic gases. However, even the most up-to-date models based on such mechanisms can not account for the SOA mass observed in the atmosphere, suggesting the existence of other, yet unknown formation processes. The present study shows experimental evidence that particulate phase chemistry produces photo-sensitizers that lead to photo-induced formation and growth of secondary organic aerosol in the near UV and the presence of volatile organic compounds (VOC) such as terpenes. By means of an aerosol flow tube reactor equipped with Scanning Mobility Particle Sizer (SMPS) having Kr-85 source aerosol neutralizer, Differential Mobility Analyser (DMA) and Condensation Particle Sizer (CPC), we identified that traces of the aerosol phase product of glyoxal chemistry as is explained in Gallway et al., and Yu et al., namely imidazole-2-carboxaldehyde (IC) is a strong photo-sensitizer when irradiated by near-UV in the presence of volatile organic compounds such as terpenes. Furthermore, the influence of pH, type and concentration of VOCs, composition of seed particles, relative humidity and irradiation intensity on particle growth were studied. This novel photo-sensitizer contributed to more than 30% of SOA growth in 19min irradiation time in the presence of terpenes in the
Tien, Yueh-Hsuan; Hsu, Min-Tao
The purpose of this study was to explore in a Taiwanese cultural context and on the basis of analysis of narrative data the illness experience of women with epilepsy and their interpretation of life after being diagnosed with epilepsy. The narrative data were obtained by in-depth interviews of ten women with epilepsy. The theme of "comparing oneself with others" emerged. Both the social stigma of epilepsy and the cultural ideology of women were identified as major issues of their life world, their interpretation revealing the suffering caused by others' social perspectives on such a stigmatized disease and their own feelings of not fulfilling the woman's role. As the research findings indicate, the women not only faced epilepsy itself, but also substantial stress from Chinese traditional culture's demand that women produce a male family heir, and from the social stereotype attached to epilepsy. The researcher recommends that these cultural impacts be incorporated into nursing assessment and treatment practices.
Grigg-Damberger, Madeleine M; Ralls, Frank
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.
Yong, L; Chengye, J; Jiong, Q
To explore the level of, and factors affecting the quality of life (QOL) in childhood epilepsy in China. At the Peking University First Hospital, we consecutively identified 418 parents whose children were with known epilepsy to complete a questionnaire, which included children's demographic characteristics, clinical message of epilepsy, QOL, familial message, parental symptoms of anxiety/depression. Significant (p<0.05) affecting factors of children's quality of life included current educational degree, mental development, age at diagnosis, age at onset, seizure frequency, duration, AED number; parental significant (p<0.05) affecting factors included anxiety, depression and health. On regression analysis, parental anxiety was the most important factor in explaining lower QOL in childhood epilepsy. AEDs, familial economic state, paternal career, seizure frequency were also significant factors. Parental anxiety outweighed the physical factors in determining QOL in childhood epilepsy. Recognition of this will be helpful for professionals to treat disease and improve the QOL of childhood epilepsy.
Singh, Anuradha; Trevick, Stephen
The International League Against Epilepsy defines epilepsy as at least 2 unprovoked seizures more than 24 hours apart. It is a wide-reaching and complex illness affecting more than 70 million people worldwide and can take on a variety of forms, patterns, and severities. Geographic differences in the illness are often related to its etiology. A host of endemic illnesses and parasitic infections can lead to epilepsy syndromes. Management varies by region due to the availability of diagnostic modalities and medications. Treatment gaps in epilepsy care often are related to social and cultural factors that must also be understood. Copyright © 2016 Elsevier Inc. All rights reserved.
Pruna, Dario; Balestri, Paolo; Zamponi, Nelia; Grosso, Salvatore; Gobbi, Giuseppe; Romeo, Antonino; Franzoni, Emilio; Osti, Maria; Capovilla, Giuseppe; Longhi, Riccardo; Verrotti, Alberto
Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.
Hesdorffer, Dale C; Ishihara, Lianna; Webb, David J; Mynepalli, Lakshmi; Galwey, Nicholas W; Hauser, W Allen
People with epilepsy have a 5-fold increased risk of suicide. Less is known about attempted suicide and whether psychiatric disorders and antiepileptic drugs modify the risk of attempted suicide. To estimate the magnitude of the association between attempted suicide and epilepsy by comparing a first suicide attempt and a second suicide attempt (hereafter referred to as a recurrent suicide attempt) among people before they received a diagnosis of epilepsy (case patients) with a first suicide attempt and a recurrent suicide attempt among people without epilepsy (control patients), and to evaluate the effect of comorbid psychiatric disorders and the exclusion of antiepileptic drug prescriptions on this association. Population-based retrospective cohort study in the United Kingdom of case patients with incident epilepsy and control patients without a history of epilepsy in a general practice setting using Clinical Practice Research Datalink. The case patients with incident epilepsy were identified between 1987 and 2013 and were 10 to 60 years of age. The control patients for each case patient were 4 randomly selected people who did not receive a diagnosis of epilepsy before the case patient's epilepsy was diagnosed (the index date), matched by year of birth, sex, and general practice for a control to case ratio of 4 to 1. Hazard ratio for incident and recurrent suicide attempts among case patients with epilepsy compared with control patients without. For 14,059 case patients (median age, 36 years [range, 10-60 years]) who later had an onset of epilepsy vs 56,184 control patients (median age, 36 years [range, 10-60 years]), the risk was increased 2.9-fold (95% CI, 2.5- to 3.4-fold) for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy. For 278 case patients (median age, 37 years [range, 10-61 years]) who later had an onset of epilepsy vs 434 control patients (median age, 35 years [range, 11-61 years]), the risk was
Aaberg, Kari Modalsli; Surén, Pål; Søraas, Camilla Lund; Bakken, Inger Johanne; Lossius, Morten I; Stoltenberg, Camilla; Chin, Richard
The study provides updated information about the distribution of seizures, epilepsies, and etiologies of epilepsy in the general child population, and compares the old and new classification systems from the International League Against Epilepsy (ILAE). The study platform was the Norwegian Mother and Child Cohort Study. Cases of epilepsy were identified through registry linkages and sequential parental questionnaires. Epilepsy diagnoses were validated using a standardized protocol, and seizures, epilepsies, and etiologies were classified according to the old (ILAE 1981/1989) and new (ILAE 2017) classifications. Information was collected through medical record reviews and/or parental telephone interviews. The study population included 112,744 children aged 3-13 years at the end of follow-up on December 31, 2012. Of these, there were 606 children with epilepsy (CWE). Distribution of seizure types varied by age of onset. Multiple seizure types were common with early onset. Focal epilepsies were the most common, occurring in 317 per 100,000 children in the study population and in 59% of CWE. Generalized epilepsies were found in 190 per 100,000 (35% of CWE). CWE with onset during the first 2 years of life had an even distribution of focal and generalized epilepsies, whereas focal epilepsies became dominant at later ages of onset. A definite cause of epilepsy had been demonstrated in 33% of CWE. The ILAE 1989 classification allowed for a broad syndrome category in 93% of CWE and a defined epileptic syndrome in 37%. With the ILAE 2017 classification, 41% of CWE had a defined epileptic syndrome and 63% had either a defined syndrome or structural-metabolic etiology. The distribution of seizures and epilepsies is strongly dependent on age of onset. Despite diagnostic advances, the causes of epilepsy are still unknown in two-thirds of CWE. The ILAE 2017 classifications allow for a higher precision of diagnoses, but at the expense of leaving more epilepsies classifiable only
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
Manonmani, V; Wallace, S J
The cases are described of eight children, five of them girls, who had epilepsy with myoclonic absences. The mean age of onset was 4.9 years. Brief episodes of loss of awareness with bilateral clonic jerking of the upper limbs were associated with rhythmic 3 cycles/second spike-wave discharges on electroencephalogram. Generalised tonic-clonic or astatic seizures, or both, also occurred in seven patients. All now have learning difficulties, and seven have behavioural problems. Conventional treatment for absences was effective in only two children. Of six patients treated with lamotrigine, five have improved substantially, but only one is in sustained complete remission. One recently diagnosed patient continues to have frequent myoclonic absences. As the response to treatment and long term outcome are much poorer, it is important to differentiate myoclonic absences from typical childhood absence epilepsy. PMID:8185360
Pharmacological treatment is the mainstay for the treatment of epilepsy. However concerns regarding long-term side effects of drugs are increasingly voiced. Behavioral treatments including biofeedback, represents an alternative management option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral procedure through which patients can learn to gain psychophysiological control over seizures. This article will first overview seizure precipitation from a psychological perspective, and then introduce three major biofeedback treatments. Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses electroencephalographic parameters and are categorized as neurofeedback. Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral sympathetic tone. The neural mechanisms underlying biofeedback treatment will be discussed in relation to thalamo-cortical regulation(of neural excitability across brain networks).
Rosenberg, Evan C.; Patra, Pabitra H.; Whalley, Benjamin J.
cannabinoids, most notably cannabidiol (CBD) and cannabidavarin (CBDV), in models of seizures, epilepsy, epileptogenesis, and neuroprotection are less ambiguous, and consistent with reports of therapeutically beneficial effects of these compounds in clinical studies. However, continued paucity of firm information regarding the therapeutic molecular mechanism of CBD/CBDV highlights the continued need for research in this area in order to identify as yet under-exploited targets for drug development and raise our understanding of treatment-resistant epilepsies. The recent reporting of positive results for cannabidiol treatment in two Phase III clinical trials in treatment-resistant epilepsies provides pivotal evidence of clinical efficacy for one plant cannabinoid in epilepsy. Moreover, risks and/or benefits associated with the use of unlicensed Δ9-THC containing marijuana extracts in pediatric epilepsies remain poorly understood. Therefore, in light of these paradigm-changing clinical events, the present review's findings aim to drive future drug development for newly-identified targets and indications, identify important limitations of animal models in the investigation of plant cannabinoid effects in the epilepsies, and focuses future research in this area on specific, unanswered questions regarding the complexities of endocannabinoid signaling in epilepsy. PMID:28190698
Delmis, J; Drazancić, A; Tkalcević, T; Ivanisević, M
A total of 132 women with epilepsy were confined in the period from 1978-1989. Their pregnancies and outcomes were analysed. The special aim was to find out if the anticonvulsive therapy has any correlation with the occurrence of fetal malformations in the studied group of women. In 43.9% of pregnant women with epilepsy, methyl-phenobarbitone as an anticonvulsive drug was administered, while carbamazepine was applied in 13.6% cases. A combination of phenytoin and phenobarbitone was prescribed in 18.9% of cases. Primidone was the drug of choice in 8% cases and 5.3% of patients were treated with various combinations of anticonvulsive drugs. Hyperemesis, threatened spontaneous abortion and premature labor complicated significantly more pregnancies in patients with epilepsy than on controls. Pregnancies from the studied group were terminated by the cesarean section in significantly more cases (11.2%) than in the control group (5.4%). Newborns from mothers with epilepsy had a statistically lower birthweight (3173 +/- 575 g) than those born from healthy mothers (3376 +/- 510g). Fifteen newborns or 11.2% were born with congenital malformations, while among the control group of newborns only two were malformed. It is noticed that the newborns from mothers treated with phenitoin and phenobarbitone had dysmorphic anomalies of the face more frequently. The drugs mentioned above interfere with the metabolism of K vitamin and as a result of this interreaction, mothers and newborns can suffer from coagulation disorders. In conclusion it is important to mention that no anticonvulsant drug seems to be absolutely safe when used during pregnancy since each of them has a teratogenic effect on the fetus.
Aluminum phthalocyanine (AlPc) is a second-generation photosensitizer under study for photodynamic therapy (PDT) of cancer. Its mechanism of action is not known. Fluoride appears to be a powerful probe for the mechanistic study of AlPc derivatives. F- forms a complex with the Al ligand, resulting in drastically reduced AlPc-induced phototoxicity. This is due to a modified binding of AlPc with certain target proteins, resulting in inhibition of electron transfer reactions (type I) but not singlet oxygen reactions (type II). In Chinese hamster ovary (CHO) cell membranes, Na+/K+-ATPase activity is selectively protected by F- from photosensitized inhibition by AlPc, suggesting that this enzyme may be a critical target for AlPc-PDT. Another cellular response, not interfered with by F-, is a transient increase of cytoplasmic free Ca2+ after AlPc-PDT. This increase was shown to trigger the induction of a recovery process.
Aubertin, Kelly; Bonneau, Stéphanie; Silva, Amanda K. A.; Bacri, Jean-Claude; Gallet, François; Wilhelm, Claire
The intracellular microenvironment is essential for the efficiency of photo-induced therapies, as short-lived reactive oxygen species generated must diffuse through their intracellular surrounding medium to reach their cellular target. Here, by combining measurements of local cytoplasmic dissipation and active trafficking, we found that photosensitizers activation induced small changes in surrounding viscosity but a massive decrease in diffusion. These effects are the signature of a return to thermodynamic equilibrium of the system after photo-activation and correlated with depolymerization of the microtubule network, as shown in a reconstituted system. These mechanical measurements were performed with two intracellular photosensitizing chlorins having similar quantum yield of singlet oxygen production but different intracellular localizations (cytoplasmic for mTHPC, endosomal for TPCS2a). These two agents demonstrated different intracellular impact. PMID:24386423
Seburg, Randal A; Ballard, John M; Hwang, Tsang-Lin; Sullivan, Caitlin M
During development of an extemporaneous suspension formulation for losartan potassium, previously unknown degradation products were observed in experimental suspensions prepared in a commercial cherry syrup vehicle. These degradates increased rapidly when analytical solutions prepared from that suspension were exposed to ambient light. The structures of the degradates were determined using a combination of preparative HPLC, LC/MS, (13)C and (1)H NMR (1D and 2D), and mechanistic chemistry. Each degradate results from destruction of the imidazole ring of losartan. Formation of the two major degradates required exposure to light (UV or visible) and the presence of oxygen. Experiments using Rose Bengal (a singlet oxygen photosensitizer) and 1,4-diazabicyclooctane (DABCO; a singlet oxygen quencher) established that the major photodegradates are formed via the intermediacy of singlet oxygen. The identity of the photosensitizer in the formulation was not unequivocally determined; however, the experiments implicated the artificial flavoring in fulfilling this role.
Dutta, Manaswita; Murray, Laura; Miller, Wendy; Groves, Doyle
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.
Cross, J Helen
About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of additional treatments in people with drug-resistant epilepsy characterised by generalised seizures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety on the addition of the following interventions: lacosamide, lamotrigine, levetiracetam, perampanel, and zonisamide versus the addition of placebo.
Taubøll, Erik; Gjerstad, Leif; Henriksen, Tore; Husby, Henrik
Women with epilepsy have several gender-specific problems, first of all related to pregnancy and childbirth. They do, however, also meet with several other, less well-recognised specific problems. Many women have a marked change in seizure frequency in relation to their menstrual cycle, and menstrual disorders and polycystic ovaries induced by the use of antiepileptic drugs (AEDs), or by the condition itself, are more frequent in women with epilepsy. Cosmetic side effects of AEDs including weight gain, hair loss and skin problems can significantly reduce compliance in drug treatment and thus affect seizure frequency. Enzyme-inducing AEDs reduce the effectiveness of oral contraceptives and may lead to unplanned pregnancies. A higher incidence of sexual problems in women with epilepsy has also been reported. In menopause, the seizure frequency may change in parallel with the endocrine changes and some AEDs may facilitate the development of osteoporosis. Better understanding and awareness of these problems among patients and health care professionals can relieve many of the gender-specific problems in women. The goal is to tailor the treatment to the needs of the individual woman.
Saxena, V. S.; Nadkarni, V. V.
Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG) biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine). Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70–80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment. PMID:22028523
Lewis, Ann; Parsons, Sarah
There is a striking dearth of studies focusing sensitively and in depth on the mainstream educational experiences of children with epilepsy, as viewed by those children themselves. The one-year project (2006-7) reported here addresses that gap. Children's perceptions about mainstream teachers' understanding of epilepsy and school-based needs are…
Dash, Deepa; Tripathi, Manjari
Extratemporal lobe epilepsies (ETLE) are characterized by the epileptogenic foci outside the temporal lobe. They have a wide spectrum of semiological presentation depending upon the site of origin. They can arise from frontal, parietal, occipital lobes and from hypothalamic hamartoma. We discuss in this review the semiology of different types of ETLE encountered in the epilepsy monitoring unit. PMID:24791090
Adam, David; Bösche, Lisa; Castañeda-Losada, Leonardo; Winkler, Martin; Apfel, Ulf-Peter; Happe, Thomas
We report a sustainable in vitro system for enzyme-based photohydrogen production. The [FeFe]-hydrogenase HydA1 from Chlamydomonas reinhardtii was tested for photohydrogen production as a proton-reducing catalyst in combination with eight different photosensitizers. Using the organic dye 5-carboxyeosin as a photosensitizer and plant-type ferredoxin PetF as an electron mediator, HydA1 achieves the highest light-driven turnover number (TON HydA1 ) yet reported for an enzyme-based in vitro system (2.9×10 6 mol(H 2 ) mol(cat) -1 ) and a maximum turnover frequency (TOF HydA1 ) of 550 mol(H 2 ) mol(HydA1) -1 s -1 . The system is fueled very effectively by ambient daylight and can be further simplified by using 5-carboxyeosin and HydA1 as a two-component photosensitizer/biocatalyst system without an additional redox mediator. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Lagunes, Irene; Vázquez-Ortega, Fernanda; Trigos, Ángel
Moderate consumption of red wine provides beneficial effects to health. This is attributed to polyphenol compounds present in wine such as resveratrol, quercetin, gallic acid, rutin, and vanillic acid. The amount of these antioxidants is variable; nevertheless, the main beneficial effects of red wine are attributed to resveratrol. However, it has been found that resveratrol and quercetin are able to photosensitize singlet oxygen generation and conversely, gallic acid acts as quencher. Therefore, and since resveratrol and quercetin are some of the most important antioxidants reported in red wines, the aim of this research was to evaluate the photosensitizing ability of 12 red wine extracts through photo-oxidation of ergosterol. The presence of 1 O 2 was detected by ergosterol conversion into peroxide of ergosterol through 1 H NMR analysis. Our results showed that 10 wine extracts were able to act as photosensitizers in the generation of singlet oxygen. The presence of 1 O 2 can damage other compounds of red wine and cause possible organoleptic alterations. Finally, although the reaction conditions employed in this research do not resemble the inherent conditions in wine making processing or storing, or even during its consumption, this knowledge could be useful to prevent possible pro-oxidant effects and avoid detrimental effects in red wines. © 2017 Institute of Food Technologists®.
Land, Cecil E.; Peercy, Paul S.
The photosensitivity of lead lanthanum zirconate titanate (PLZT) ceramic material used in high resolution, high contrast, and non-volatile photoferroelectric image storage and display devices is enhanced significantly by positive ion implantation of the PLZT near its surface. Implanted ions include H.sup.+, He.sup.+, Ne.sup.+, Ar.sup.+, as well as chemically reactive ions from Fe, Cr, and Al. The positive ion implantation advantageously serves to shift the absorption characteristics of the PLZT material from near-UV light to visible light. As a result, photosensitivity enhancement is such that the positive ion implanted PLZT plate is sensitive even to sunlight and conventional room lighting, such as fluorescent and incandescent light sources. The method disclosed includes exposing the PLZT plate to the positive ions at sufficient density, from 1.times.10.sup.12 to 1.times.10.sup.17, and with sufficient energy, from 100 to 500 KeV, to provide photosensitivity enhancement. The PLZT material may have a lanthanum content ranging from 5 to 10%, a lead zirconate content of 62 to 70 mole %, and a lead titanate content of 38 to 30%. The ions are implanted at a depth of 0.1 to 2 microns below the surface of the PLZT plate.
Judy, Millard M.; Sogandares-Bernal, Franklin M.; Matthews, James Lester
Blood-borne viruses and protozoan parasites that are infectious to humans pose risk world-wide of infection transmission through blood and blood product transfusion. Blood-borne infectious viruses include human immunodeficiency virus (HIV-I), which causes AIDS; hepatitis C virus, which can cause chronic hepatitis; and cytomegalovirus, which can be dangerous to immunocompromised patients, e.g., the newborn, transplant recipients, and AIDS patients. Infectious blood-borne protozoan parasites include Trypanosoma cruzi, which causes Chagas' disease, endemic throughout Central and South America; the Trypanosoma species causing African sleeping sickness endemic in Central Africa; and Plasmodium falciparum, which causes malignant and increasingly drug- resistant human malaria prevalent throughout the tropics. Some researchers have focused on using photosensitizers to inactivate HIV-I and other viruses in whole blood, packed red cells, and platelet concentrates without compromising blood product function. Our group previously has reported photosensitized in vitro inactivation of P. falciparum and the mouse malaria organism Plasmodium berghei in whole blood using hematoporphyrin derivative (HPD) and of T. cruzi using benzoporphyrin derivatives BPDMA and BPDDA, dihematoporphyrin ether (DHE), and hydroxyethylvinyldeuteroporphyrin (HEVD). These results suggest that continued investigation is warranted to evaluate the potential for photosensitized inactivation of blood-borne parasites in blood banking.
Valkov, Anton; Nakonechny, Faina; Nisnevitch, Marina
The photosensitizers Rose Bengal (RB) and methylene blue (MB), when immobilized in polystyrene, were found to exhibit high antibacterial activity in a continuous regime. The photosensitizers were immobilized by dissolution in chloroform, together with polystyrene, with further evaporation of the solvent, yielding thin polymeric films. Shallow reservoirs, bottom-covered with these films, were used for constructing continuous-flow photoreactors for the eradication of Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli and wastewater bacteria under illumination with visible white light using a luminescent lamp at a 1.8 mW·cm−2 fluence rate. The bacterial concentration decreased by two to five orders of magnitude in separate reactors with either immobilized RB or MB, as well as in three reactors connected in series, which contained one of the photosensitizers. Bacterial eradication reached more than five orders of magnitude in two reactors connected in series, where the first reactor contained immobilized RB and the second contained immobilized MB. PMID:25158236
Davies, Kellie S; Linder, Michelle K; Kryman, Mark W; Detty, Michael R
Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M). Copyright © 2016 Elsevier Ltd. All rights reserved.
Vendrell-Criado, Victoria; Rodríguez-Muñiz, Gemma M; Lhiaubet-Vallet, Virginie; Cuquerella, M Consuelo; Miranda, Miguel A
Based on our previous investigations into the photophysical properties of the 5-methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1) , and a triplet-excited-state energy of 297 kJ mol(-1) . Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 μs, and a high formation quantum yield, ΦISC =0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Teich, Monique; van Pinxteren, Dominik; Kecorius, Simonas; Wang, Zhibin; Herrmann, Hartmut
Imidazoles are widely discussed in recent literature. They have been studied as a secondary product of the reaction of dicarbonyls with nitrogen containing compounds in a number of laboratory studies, potentially acting as photosensitizers triggering secondary organic aerosol growth and are forming constituents of light absorbing brown carbon. Despite the knowledge from laboratory studies, no quantitative information about imidazoles in ambient aerosol particles is available. Within the present study, five imidazoles (1-butylimidazole, 1-ethylimidazole, 2-ethylimidazole, imidazol-2-carboxaldehyde, and 4(5)-methylimidazole) were successfully identified and quantified for the first time in ambient aerosol samples from different environments in Europe and China. Their concentrations range between 0.2 and 14 ng/m(3). 4(5)-Methylimidazole was found to be the most abundant imidazole. The occurrence of imidazoles seems to be favored at sites with strong biomass burning influence or connected to more polluted air masses. No connection was found between aerosol particle pH and imidazole concentration. Our work corroborates the laboratory studies by showing that imidazoles are present in ambient aerosol samples in measurable amounts. Moreover, it further motivates to explore the potential photosensitizing properties of small alkyl-substituted imidazoles.
Huang, Lisu; Li, Shi; He, Dake; Bao, Weiqun; Li, Ling
This study aimed to investigate early predictors (6 months after diagnosis) of medical intractability in epilepsy. All children <12 years of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital between 1992 and 2006 were included. Medical intractability was defined as failure, due to lack of seizure control, of more than 2 antiepileptic drugs at maximum tolerated doses, with an average of more than 1 seizure per month for 24 months and no more than 3 consecutive months of seizure freedom during this interval. Univariate and multivariate logistic regression models were performed to determine the risk factors for developing medical intractability. Receiver operating characteristic curve was applied to fit the best compounded predictive model. A total of 649 patients were identified, out of which 119 (18%) met the study definition of intractable epilepsy at 2 years after diagnosis, and the rate of intractable epilepsy in patients with idiopathic syndromes was 12%. Multivariate logistic regression analysis revealed that neurodevelopmental delay, symptomatic etiology, partial seizures, and more than 10 seizures before diagnosis were significant and independent risk factors for intractable epilepsy. The best model to predict medical intractability in epilepsy comprised neurological physical abnormality, age at onset of epilepsy under 1 year, more than 10 seizures before diagnosis, and partial epilepsy, and the area under receiver operating characteristic curve was 0.7797. This model also fitted best in patients with idiopathic syndromes. A predictive model of medically intractable epilepsy composed of only four characteristics is established. This model is comparatively accurate and simple to apply clinically. Copyright © 2014 Elsevier Inc. All rights reserved.
Hsu, David A; Rayer, Katherine; Jackson, Daren C; Stafstrom, Carl E; Hsu, Murielle; Ferrazzano, Peter A; Dabbs, Kevin; Worrell, Gregory A; Jones, Jana E; Hermann, Bruce P
To determine correlations of the EEG frequency spectrum with neuropsychological status in children with idiopathic epilepsy. Forty-six children ages 8-18 years old with idiopathic epilepsy were retrospectively identified and analyzed for correlations between EEG spectra and neuropsychological status using multivariate linear regression. In addition, the theta/beta ratio, which has been suggested as a clinically useful EEG marker of attention-deficit hyperactivity disorder (ADHD), and an EEG spike count were calculated for each subject. Neuropsychological status was highly correlated with posterior alpha (8-15 Hz) EEG activity in a complex way, with both positive and negative correlations at lower and higher alpha frequency sub-bands for each cognitive task in a pattern that depends on the specific cognitive task. In addition, the theta/beta ratio was a specific but insensitive indicator of ADHD status in children with epilepsy; most children both with and without epilepsy have normal theta/beta ratios. The spike count showed no correlations with neuropsychological status. (1) The alpha rhythm may have at least two sub-bands which serve different purposes. (2) The theta/beta ratio is not a sensitive indicator of ADHD status in children with epilepsy. (3) The EEG frequency spectrum correlates more robustly with neuropsychological status than spike count analysis in children with idiopathic epilepsy. (1) The role of posterior alpha rhythms in cognition is complex and can be overlooked if EEG spectral resolution is too coarse or if neuropsychological status is assessed too narrowly. (2) ADHD in children with idiopathic epilepsy may involve different mechanisms from those in children without epilepsy. (3) Reliable correlations with neuropsychological status require longer EEG samples when using spike count analysis than when using frequency spectra. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights
Mlinar, Simona; Petek, Davorina; Cotič, Živa; Mencin Čeplak, Metka; Zaletel, Marjan
Background. Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. Methods. This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. Results. Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE's social network, which leads to (self-)isolation and social distrust. Conclusion. PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy. PMID:27212802
Zis, Panagiotis; Siatouni, Anna; Kimiskidis, Vassilios K; Verentzioti, Anastasia; Kefalonitis, Georgios; Triantafyllou, Nikolaos; Gatzonis, Stylianos
Regulations and guidelines regarding driving privileges of patients with epilepsy vary greatly worldwide. The aim of our study was twofold: firstly, to evaluate disobedient drivers in Greece and to elucidate their awareness of the law, emotional responses, and seizure profile and, secondly, to identify determinants of disobedience regarding driving among patients with epilepsy. All consecutive patients with epilepsy who visited the epilepsy outpatient clinic of two tertiary epilepsy centers were invited to participate in the study. One hundred ninety patients met our inclusion criteria. Fifty-two percent of our study population was aware of the driving restrictions. More than one out of three patients were disobedient (35.8%). Being a male was associated with a 6.07-fold increase in the odds of being disobedient (95% CI: 2.73-13.47, p < 0.001); being employed was associated with a 4.62-fold increase in the odds of being disobedient (95% CI: 2.20-9.68, p < 0.001); and each extra antiepileptic drug (AED) was associated with a decrease in the odds of disobedience by a factor of 0.41 (95% CI: 0.26-0.63, p < 0.001). Male gender, employment, and number of AEDs are important determinants of disobedience regarding driving among patients with epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.
Carlsson, Malin; Olsson, Ingrid; Hagberg, Gudrun; Beckung, Eva
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.
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
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
Barker-Haliski, Melissa L; Johnson, Kristina; Billingsley, Peggy; Huff, Jennifer; Handy, Laura J; Khaleel, Rizvana; Lu, Zhenmei; Mau, Matthew J; Pruess, Timothy H; Rueda, Carlos; Saunders, Gerald; Underwood, Tristan K; Vanegas, Fabiola; Smith, Misty D; West, Peter J; Wilcox, Karen S
The successful identification of promising investigational therapies for the treatment of epilepsy can be credited to the use of numerous animal models of seizure and epilepsy for over 80 years. In this time, the maximal electroshock test in mice and rats, the subcutaneous pentylenetetrazol test in mice and rats, and more recently the 6 Hz assay in mice, have been utilized as primary models of electrically or chemically-evoked seizures in neurologically intact rodents. In addition, rodent kindling models, in which chronic network hyperexcitability has developed, have been used to identify new agents. It is clear that this traditional screening approach has greatly expanded the number of marketed drugs available to manage the symptomatic seizures associated with epilepsy. In spite of the numerous antiseizure drugs (ASDs) on the market today, the fact remains that nearly 30% of patients are resistant to these currently available medications. To address this unmet medical need, the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) revised its approach to the early evaluation of investigational agents for the treatment of epilepsy in 2015 to include a focus on preclinical approaches to model pharmacoresistant seizures. This present report highlights the in vivo and in vitro findings associated with the initial pharmacological validation of this testing approach using a number of mechanistically diverse, commercially available antiseizure drugs, as well as several probe compounds that are of potential mechanistic interest to the clinical management of epilepsy.
Reddy, Doodipala Samba; Golub, Victoria M
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.
Sherman, Elisabeth M S; Brooks, Brian L; Fay-McClymont, Taryn B; MacAllister, William S
children with epilepsy were highest on visual and verbal subtests measuring reasoning skills such as Matrix Reasoning, and lowest on Coding (mean 5.93, SD 3.6). In terms of percentage of children on each subtest with low scores (i.e., scores below 2 SDs from the expected normative mean of 10), the Coding subtest identified the most children (28.3%) with low scores, and the Similarities subtest identified the fewest (16%). Later age at onset and shorter epilepsy duration were both correlated with higher WISC-IV FSIQ and index scores (r correlation coefficient values ranging from 0.36 to 0.44, p < 0.0001), and number of current and previous antiepileptic drug trials were both inversely correlated with FSIQ and index scores (r -0.27 to -0.47, all p-values < 0.01). Neither the FSIQ nor the index scores were significantly related to seizure frequency. A similar pattern was found for subtest scores. No differences in FSIQ, index scores, or subtest scores were found between children with left- and right-hemisphere seizure foci, or between those with positive or negative magnetic resonance imaging (MRI) findings. The WISC-IV is sensitive to epilepsy-related cognitive problems in clinically referred children with high seizure burden, particularly problems relating to expressive verbal, working memory, and processing speed difficulties. Compared to healthy children, these children have a very high rate of cognitive difficulties as assessed by the WISC-IV. The usefulness of the WISC-IV in detecting cognitive deficits in children with milder forms of epilepsy remains to be determined. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.
Doumlele, Kyra; Friedman, Daniel; Buchhalter, Jeffrey; Donner, Elizabeth J; Louik, Jay; Devinsky, Orrin
Children with benign epilepsy with centrotemporal spikes (BECTS) have traditionally been considered to have a uniformly good prognosis. However, benign may be a misnomer because BECTS is linked to cognitive deficits, a more severe phenotype with intractable seizures, and the potential for sudden unexpected death in epilepsy (SUDEP). To determine if cases of BECTS are present in the North American SUDEP Registry (NASR). The NASR is a clinical and biospecimen repository established in 2011 to promote SUDEP research. The NASR database, which includes medical records, results of electroencephalographic tests, and interviews with family members of patients with epilepsy who died suddenly without other identifiable causes of death, was queried from June 3, 2011, to June 3, 2016, for cases of BECTS. The patients with epilepsy had died suddenly without other identifiable causes of death (eg, drowning, trauma, exposure to toxic substances, or suicide); SUDEP classification was determined by the consensus of 2 epileptologists. Cases of SUDEP among children who received a diagnosis of BECTS among patients reported in the NASR. Three boys (median age at death, 12 years; range, 9-13 years) who received a diagnosis of BECTS by their pediatric epileptologist or neurologists were identified among 189 cases reported in the NASR. The median age of epilepsy onset was 5 years (range, 3-11 years), and the median duration of epilepsy was 4 years (range, 1-10 years). Two deaths were definite SUDEP, and 1 was probable SUDEP. Independent review of clinical and electroencephalographic data supported the diagnosis of BECTS in all 3 patients. None of the patients was prescribed antiseizure drugs, either owing to physician recommendation or mutual decision by the physician and parents. All 3 patients were found dead in circumstances typical of SUDEP. The 3 patients spanned the spectrum of BECTS severity: 1 had only a few seizures, 1 had more than 30 focal motor seizures, and 1 had 4 witnessed
Nagai, H; Shikata, A; Sato, N; Takeuchi, Y; Sawada, T
We report an 11-year-old boy with a non-photosensitive epileptic self-induced seizures, pacygyria and familial ataxia. His grandmother and aunts had dysarthria, and his mother had developed progressive ataxia and myoclonus since 40 years old. His older sister had ataxia, mental retardation and epilepsy. As for the boy, motor developmental delay with muscle hypertonicity of left extremities was recognized at the age of 5 months. Mental retardation and ataxia was recognized at the age of 3 years and slight mental regression is recognized at the age of 11 years. No special findings were detected in an examination of his blood and cerebrospinal fluid, including amino acids, lysosomal enzymes activity and genetic analysis for dentatorubralpallidoluysian atrophy. Brain magnetic resonance imaging revealed pachygyria of the right cerebral cortecies. At the age of two, he began to induce seizures with impairment of consciousness in himself by waving his right hand over his face which was directed toward a source of bright light. At the age of seven, he developed spontaneous seizures with impairment of consciousness. An EEG showed frequent spikes in the occipital areas, on the right and left sides occurring either independently or synchronously. Intermittent photic stimulation and pattern stimulation did not induce a paroxysmal discharge in EEG. Ictal EEG suggested that the origin of the seizures was the occipital lobe. Treatment with valporate and zonisamide was effective in reducing the seizures. The findings of our case imply the pathogenesis of self-induced seizures and the relationship between PME and neuronal migration disorders.
Kerr, M.; Scheepers, M.; Arvio, M.; Beavis, J.; Brandt, C.; Brown, S.; Huber, B.; Iivanainen, M.; Louisse, A. C.; Martin, P.; Marson, A. G.; Prasher, V.; Singh, B. K.; Veendrick, M.; Wallace, R. A.
Background: Epilepsy has a pervasive impact on the lives of people with intellectual disability and their carers. The delivery of high-quality care is impacted on by the complexity and diversity of epilepsy in this population. This article presents the results of a consensus clinical guideline process. Results: A Delphi process identified a list…
Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura
Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Sahoo, Satya S.; Zhang, Guo-Qiang; Lhatoo, Samden D.
Summary The epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology-driven informatics infrastructure and its role in adoption of a “data-driven” paradigm in epilepsy research. PMID:23647220
Osakwe, Chijioke; Otte, Willem M; Alo, Chimhurumnanya
Epilepsy is a common neurological disorder in Nigeria. Many individuals are affected in rural areas, although prevalence data is not available. In this study we aimed to establish the prevalence of epilepsy in a rural community in south-east Nigeria, a community suspected for having a high number of people living with epilepsy. We compared this with the prevalence in a nearby semi-urban community in north-central Nigeria. In both communities we identified potential causes of epilepsy and obtained information on the social beliefs regarding epilepsy. We used door-to-door surveys and focus group discussions. The epilepsy prevalence in the rural community was 20.8/1000 [95% confidence interval (CI): 15.7-27.4]. The prevalence in the semi-rural community was lower, namely 4.7/1000 [CI: 3.2-6.9]. The difference in prevalence was highly significant (χ(2)-test, p<0.0001). In both communities most people with epilepsy were in the age range of 7-24 years. Causes that might be contributory to the prevalence of epilepsy in both communities included poor obstetric practices, frequent febrile convulsions, head trauma, meningitis and neurocysticercosis. In both communities we found stigma of people with epilepsy. In conclusion, the epilepsy prevalence in the semi-urban community is similar to that in industrialized countries. In contrast, the rural community has a much higher prevalence. This may require the establishment of specific community-based epilepsy control programs. Community interventions should focus on treatment of acute epilepsy and on stigma reduction. Copyright © 2013 Elsevier B.V. All rights reserved.
Law, N; Smith, M L; Widjaja, E
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
Bruno, Elisa; Bartoloni, Alessandro; Zammarchi, Lorenzo; Strohmeyer, Marianne; Bartalesi, Filippo; Bustos, Javier A; Santivañez, Saul; García, Héctor H; Nicoletti, Alessandra
The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature. Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies. The median LTE prevalence was 15.8/1,000 (95% CI 13.5-18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4-13.2), the median incidence was 138.2/100,000 (95% CI 83.6-206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01-6.1) and the overall estimated TG was 60.6% (95% CI 45.3-74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0-39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9-4.0). A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies.
The aim of the medical treatment of childhood epilepsy is to control seizures as best as possible without any significant adverse event. Treatment includes classical and new antiepileptic drugs and ketogenic diet as well The drug(s) selected is dependent on the epilepsy syndrome: the same drug may completely control seizures in a given syndrome, but aggravate them in another one. Drug-drug interact ons must be taken into account when polytherapy is needed because doses need to be modified. The treatment of childhood epilepsy is different from that of adult epilepsy because many epilepsy syndromes are specifically paediatric and maturational process requires to prescribe these drugs according to age and weight.
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.
... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Psychomotor epilepsy. 4... Psychomotor epilepsy. The term psychomotor epilepsy refers to a condition that is characterized by seizures... psychomotor epilepsy vary from patient to patient and in the same patient from seizure to seizure. (b) A...
Zhou, Haihua; Zou, Yingquan
The photosensitive compounds in the photosensitive coatings of positive PS plates are the diazonaphthaquinone derivatives. Some acidolysis small molecular phenolic ethers, which were synthesized by some special polyhydroxyl phenols with vinyl ethyl ether, are added in the positive diazonaphthaquinone photosensitive composition to improve its sensitivity, composed with photo-acid-generators. The effects to the photosensitivity, anti-alkali property, anti-isopropyl alcohol property, dot resolution and line resolution of the coatings are studied with different additive percent of the special phenolic ethers. In the conventional photosensitive diazonaphthaquinone systems for positive PS plates, the photosensitivity is improved without negative effects to resolution, anti-alkali and anti-isopropyl alcohol properties when added about 5% of the special acidolysis phenolic ethers, EAAE or DPHE, composed with photo-acid-generators.
Hirao, Akihiro; Sato, Shunichi; Saitoh, Daizoh; Shinomiya, Nariyoshi; Ashida, Hiroshi; Obara, Minoru
To obtain efficient antibacterial photodynamic effect in traumatic injuries such as burns, depth-resolved dosimetry of photosensitizer is required. In this study, we performed dual-wavelength photoacoustic (PA) measurement for rat burned skins injected with a photosensitizer. As a photosensitizer, methylene blue (MB) or porfimer sodium was injected into the subcutaneous tissue in rats with deep dermal burn. The wound was irradiated with red (665 nm or 630 nm) pulsed light to excite photosensitizers and green (532 nm) pulsed light to excite blood in the tissue; the latter signal was used to eliminate blood-associated component involved in the former signal. Acoustic attenuation was also compensated from the photosensitizer-associated PA signals. These signal processing was effective to obtain high-contrast image of a photosensitizer in the tissue. Behaviors of MB and porfimer sodium in the tissue were compared.
Helbig, Katherine L; Farwell Hagman, Kelly D; Shinde, Deepali N; Mroske, Cameron; Powis, Zöe; Li, Shuwei; Tang, Sha; Helbig, Ingo
To assess the yield of diagnostic exome sequencing (DES) and to characterize the molecular findings in characterized and novel disease genes in patients with epilepsy. In an unselected sample of 1,131 patients referred for DES, overall results were compared between patients with and without epilepsy. DES results were examined based on age of onset and epilepsy diagnosis. Positive/likely positive results were identified in 112/293 (38.2%) epilepsy patients compared with 210/732 (28.7%) patients without epilepsy (P = 0.004). The diagnostic yield in characterized disease genes among patients with epilepsy was 33.4% (105/314). KCNQ2, MECP2, FOXG1, IQSEC2, KMT2A, and STXBP1 were most commonly affected by de novo alterations. Patients with epileptic encephalopathies had the highest rate of positive findings (43.4%). A likely positive novel genetic etiology was proposed in 14/200 (7%) patients with epilepsy; this frequency was highest in patients with epileptic encephalopathies (17%). Three genes (COQ4, DNM1, and PURA) were initially reported as likely positive novel disease genes and were subsequently corroborated in independent peer-reviewed publications. DES with analysis and interpretation of both characterized and novel genetic etiologies is a useful diagnostic tool in epilepsy, particularly in severe early-onset epilepsy. The reporting on novel genetic etiologies may further increase the diagnostic yield.Genet Med 18 9, 898-905.
Elliott, John O; Charyton, Christine; McAuley, James W; Shneker, Bassel F
Social support from marriage has been linked with better health outcomes. Persons with epilepsy (PWE) are significantly less likely to be married than persons without epilepsy. No previous studies have examined the impact of marriage on epilepsy-related health concerns. Outpatient PWE (n=267) were asked to identify their top five concerns on the Epilepsy Foundation Concerns Index. After controlling for clinical factors (seizure frequency, age of epilepsy diagnosis and disability status) PWE who were married were significantly less likely to report "Fear of being injured during a seizure" Odds Ratio (OR) 0.33, "Holding down a job" OR 0.29, "Getting the work or education you want" OR 0.29, "Medical costs of your epilepsy" OR 0.21 and "Lack of people's understanding of epilepsy" OR 0.27. Once we controlled for both clinical factors and demographic factors only one concern "Medical costs of your epilepsy" OR 0.24 remained significant. Our findings support several theories examining the health benefits of marriage related to selection, protection and economic resources. PWE are particularly prone to economic disparities due to lower educational attainment and unemployment. Earlier intervention especially for those with childhood onset epilepsy may help mitigate these disparities and their impact on social relationships and marriage. Copyright © 2011 Elsevier B.V. All rights reserved.
Lee, Seo-Young; Jung, Ki-Young; Lee, Il Keun; Yi, Sang Do; Cho, Yong Won; Kim, Dong Wook; Hwang, Seung-Sik; Kim, Sejin
The Korean national health security system covers the entire population and all medical facilities. We aimed to estimate epilepsy prevalence, anticonvulsant utilization pattern and the cost. We identified prevalent epilepsy patients by the prescription of anticonvulsants under the diagnostic codes suggesting seizure or epilepsy from 2007 Korean National Health Insurance databases. The information of demography, residential area, the kind of medical security service reflecting economic status, anticonvulsants, and the costs was extracted. The overall prevalence of treated epilepsy patients was 2.41/1,000, and higher for men than women. The age-specific prevalence was the lowest in those in their thirties and forties. Epilepsy was more prevalent among lower-income individuals receiving medical aid. The regional prevalence was the highest in Jeju Island and lowest in Ulsan city. New anticonvulsants were more frequently used than old anticonvulsants in the younger age group. The total annual cost of epilepsy or seizure reached 0.46% of total medical expenditure and 0.27% of total expenditure on health. This is the first nationwide epidemiological report issued on epilepsy in Korea. Epilepsy prevalence in Korea is comparable to those in developed countries. Economic status and geography affect the prevalence of epilepsy.
Escalaya, Alejandro L; Burneo, Jorge G
There is increasing evidence of the existence of refractoriness to treatment with antiepileptic medications in those with NCC-related epilepsy. We performed a systematic review with the objective to determine the role of a cysticercotic lesion in this group of patients. We sought those manuscripts, including case reports, describing patients with NCC-related medically-intractable epilepsy who underwent epilepsy surgery and were seizure-free a year after. Only 10 manuscripts fulfilled inclusion and exclusion criteria. Three different clinical presentations were identified: 1) the cysticercotic lesion was epileptogenic, 2) there was dual pathology, including the cysticercotic lesion, with the other lesion usually being hippocampal sclerosis, and 3) the cysticercotic lesion was not related to the epileptogenic focus. In the case of an epileptogenic cysticercotic lesion, the presence of gliosis appeared to be the culprit for epileptogenicity. More studies using large cohorts of patients might be able to confirm our findings. This article is part of a Special issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.
Tacke, M; Neubauer, B A; Gerstl, L; Roser, T; Rémi, J; Borggraefe, I
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.
Ortega-Moreno, Laura; Giráldez, Beatriz G; Soto-Insuga, Victor; Losada-Del Pozo, Rebeca; Rodrigo-Moreno, María; Alarcón-Morcillo, Cristina; Sánchez-Martín, Gema; Díaz-Gómez, Esther; Guerrero-López, Rosa; Serratosa, José M
Pediatric epilepsies are a group of disorders with a broad phenotypic spectrum that are associated with great genetic heterogeneity, thus making sequential single-gene testing an impractical basis for diagnostic strategy. The advent of next-generation sequencing has increased the success rate of epilepsy diagnosis, and targeted resequencing using genetic panels is the a most cost-effective choice. We report the results found in a group of 87 patients with epilepsy and developmental delay using targeted next generation sequencing (custom-designed Haloplex panel). Using this gene panel, we were able to identify disease-causing variants in 17 out of 87 (19.5%) analyzed patients, all found in known epilepsy-associated genes (KCNQ2, CDKL5, STXBP1, SCN1A, PCDH19, POLG, SLC2A1, ARX, ALG13, CHD2, SYNGAP1, and GRIN1). Twelve of 18 variants arose de novo and 6 were novel. The highest yield was found in patients with onset in the first years of life, especially in patients classified as having early-onset epileptic encephalopathy. Knowledge of the underlying genetic cause provides essential information on prognosis and could be used to avoid unnecessary studies, which may result in a greater diagnostic cost-effectiveness.
Jin, Jing; Chen, Rong; Xiao, Zheng
Stroke and epilepsy are two of the most common neurological disorders and share a complicated relationship. It is well established that stroke is one of the most important causes of epilepsy, particularly new-onset epilepsy among the elderly. However, post-epilepsy stroke has been overlooked. In recent years, it has been demonstrated that epilepsy patients have increased risk and mortality from stroke when compared with the general population. Additionally, it was proposed that post-epilepsy stroke might be associated with antiepileptic drugs (AEDs), epileptic seizures and the lifestyle of epileptic patients. Here, we comprehensively review the epidemiology, causes and interventions for post-epilepsy stroke.
Jones, Jana E; Siddarth, Prabha; Gurbani, Suresh; Shields, W Donald; Caplan, Rochelle
Given the FDA's warning regarding the potential connection between suicidal behavior and antiepileptic drugs, this study examined methods by which to detect suicidal ideation in children with epilepsy. It compared the sensitivity, specificity, and area under the curve for identifying children with suicidal behavior using the Child Behavior Checklist (CBCL) and a structured psychiatric interview. Parent-completed CBCLs provided behavioral problem scores on 177 children with epilepsy, aged 5-16years. Psychiatric diagnoses were made based on separate child and parent structured psychiatric interviews about the child. The children answered questions on suicidal behaviors during the interview. A clinically elevated score in the CBCL Total Problems scale and having more than one psychiatric diagnosis, irrespective of the type of diagnosis, were significant predictors and correctly classified children with suicidal ideation in 79% of the cases based on the CBCL and 80% of the cases with more than one psychiatric diagnosis. These findings indicate that elevated CBCL Total Problems scores, a commonly used instrument, can screen and identify risk for suicidal behavior in children with epilepsy. Additionally, irrespective of diagnosis, if a child with epilepsy has more than one psychiatric diagnosis, further assessment of suicidal behavior is warranted. Importantly, the results underscore the utility of having parents complete a questionnaire in the waiting room in order to identify children with epilepsy at risk for suicidal behavior. © 2013.
Alkhamees, Hadeel A; Selai, Caroline E; Shorvon, Simon D
The current survey sought to identify the religious and cultural beliefs about the causes and treatment of epilepsy in people with epilepsy from Saudi Arabia and a number of other aspects relating to the possibility of cure, coping with the condition, and public awareness. Study instruments were developed on the basis of the literature, a focus group of people with epilepsy, and feedback from people in the field with local knowledge. These were then piloted. A survey was then carried out among a total of 110 adults with epilepsy. Participants were asked to complete questionnaires inquiring into their beliefs about the causes and range of treatments used for epilepsy. Each participant was allowed to choose more than one cause and more than one treatment method. The questionnaires were administered face to face by a clinical psychologist (HAA) to improve the quality of the responses. We found that most adults with epilepsy in Saudi Arabia believe that epilepsy is a condition with multifactorial causation and for which more than one treatment method should be applied. A test from God was the most commonly ascribed cause (83% as well as 40% who believed that some cases of the illness were a punishment from God). The belief in the concept of God's will helped many in the cohort to accept their illness as part of their destiny. Ninety-six percent of the patients believed that there were also medical causes (such as an illness, brain insult, inflammation, heredity, contagion), and a similar proportion believed that there were also religious causes. Smaller proportions believed epilepsy could be due to cultural (78%) or psychosocial causes (64%). Thirty-four percent of people believed that there could be sometimes no cause, but only 2% thought that epilepsy never had any identifiable cause. Most patients did not believe that one treatment alone would help. Ninety-three percent of patients believed in medical treatment, 93% in religious treatment, and 64% in traditional
Fisher, Robert S.
Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987
Liu, Lily; Song, Changbin; Xue, Bin; Li, Jing; Wang, Junxi; Li, Jinmin
Positive type photosensitive polyimide is used as the modification layer in the thin film transistors production process. The photosensitive polyimide is not only used as the second insulating layer, it can also be used instead of a mask because of the photosensitivity. A suitable curing condition can help photosensitive polyimide form the high performance polyimide with orderly texture inside, and the performance of imidization depends on the precise control of temperature, time, and heat control during the curing process. Therefore, experiments of different stepped up heating tests are made, and the ability of protecting silicon dioxide is analyzed.
Ruiz-González, Rubén.; White, John H.; Cortajarena, Aitziber L.; Agut, Montserrat; Nonell, Santi; Flors, Cristina
Antimicrobial photodynamic therapy (aPDT) combines a photosensitizer, light and oxygen to produce reactive oxygen species (ROS), mainly singlet oxygen (1O2), to photo-oxidize important biomolecules and induce cell death. aPDT is a promising alternative to standard antimicrobial strategies, but its mechanisms of action are not well understood. One of the reasons for that is the lack of control of the photosensitizing drugs location. Here we report the use of geneticallyencoded fluorescent proteins that are also 1O2 photosensitizers to address the latter issue. First, we have chosen the red fluorescent protein TagRFP as a photosensitizer, which unlike other fluorescent proteins such as KillerRed, is able to produce 1O2 but not other ROS. TagRFP photosensitizes 1O2 with a small, but not negligible, quantum yield. In addition, we have used miniSOG, a more efficient 1O2 photosensitizing fluorescent flavoprotein that has been recently engineered from phototropin 2. We have genetically incorporated these two photosensitizers into the cytosol of E. coli and demonstrated that intracellular 1O2 is sufficient to kill bacteria. Additional assays have provided further insight into the mechanism of cell death. Photodamage seems to occur primarily in the inner membrane, and extends to the outer membrane if the photosensitizer's efficiency is high enough. These observations are markedly different to those reported for external photosensitizers, suggesting that the site where 1O2 is primarily generated proves crucial for inflicting different types of cell damage.
Wirrell, Elaine C.; Grossardt, Brandon R.; Wong-Kisiel, Lily C.-L.; Nickels, Katherine C.
Purpose To determine the incidence and classification of new-onset epilepsy, as well as the distribution of epilepsy syndromes in a population-based group of children, using the newly proposed Report of the ILAE Commission on Classification and Terminology 2005–2009. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed epilepsy from 1980–2004. For each patient, epilepsy was classified into mode of onset, etiology, and syndrome or constellation (if present). Incidence rates were calculated overall and also separately for categories of mode of onset and etiology. Results The adjusted incidence rate of new-onset epilepsy in children was 44.5 cases per 100,000 persons per year. Incidence rates were highest in the first year of life and diminished with age. Mode of onset was focal in 68%, generalized/bilateral in 23%, spasms in 3% and unknown in 5%. Approximately half of children had an unknown etiology for their epilepsy, and of the remainder, 78 (22%) were genetic and 101 (28%) were structural/metabolic. A specific epilepsy syndrome could be defined at initial diagnosis in 99/359 (28%) children, but only 9/359 (3%) had a defined constellation. Conclusion Nearly half of childhood epilepsy is of “unknown” etiology. While a small proportion of this group met criteria for a known epilepsy syndrome, 41% of all childhood epilepsy is of “unknown” cause with no clear syndrome identified. Further work is needed to define more specific etiologies for this group. PMID:21482075
van Ool, Jans S; Snoeijen-Schouwenaars, Francesca M; Schelhaas, Helenius J; Tan, In Y; Aldenkamp, Albert P; Hendriksen, Jos G M
Epilepsy is a neurological condition that is particularly common in people with intellectual disability (ID). The care for people with both epilepsy and ID is often complicated by the presence of neuropsychiatric disorders, defined as psychiatric symptoms, psychiatric disorders, and behavioral problems. The aim of this study was to investigate associations between epilepsy or epilepsy-related factors and neuropsychiatric comorbidities in patients with ID and between ID and neuropsychiatric comorbidities in patients with epilepsy. We performed a systematic review of the literature, published between January 1995 and January 2015 and retrieved from PubMed/Medline, PsycINFO, and ERIC and assessed the risk of bias using the SIGN-50 methodology. Forty-two studies were identified, fifteen of which were assessed as having a low or acceptable risk-of-bias evaluation. Neuropsychiatric comorbidities were examined in relation to epilepsy in nine studies; in relation to epilepsy-related factors, such as seizure activity, seizure type, and medication in four studies; and in relation to the presence and degree of ID in five studies. We conclude that the presence of epilepsy only was not a clear determinant of neuropsychiatric comorbidity in patients with ID, although a tendency towards negative mood symptoms was identified. Epilepsy-related factors indicating a more severe form of epilepsy were associated with neuropsychiatric comorbidity as was the presence of ID as compared to those without ID in patients with epilepsy, although this should be validated in future research. A large proportion of the studies in this area is associated with a substantial risk of bias. There is a need for high quality studies using standardized methods to enable clear conclusions to be drawn that might assist in improving the quality of care for this population. Copyright © 2016 Elsevier Inc. All rights reserved.
Tan, Michael; Wilson, Ian; Braganza, Vanessa; Ignatiadis, Sophia; Boston, Ray; Sundararajan, Vijaya; Cook, Mark J; D'Souza, Wendyl J
We report the diagnostic validity of a selection algorithm for identifying epilepsy cases. Retrospective validation study of International Classification of Diseases 10th Revision Australian Modification (ICD-10AM)-coded hospital records and pharmaceutical data sampled from 300 consecutive potential epilepsy-coded cases and 300 randomly chosen cases without epilepsy from 3/7/2012 to 10/7/2013. Two epilepsy specialists independently validated the diagnosis of epilepsy. A multivariable logistic regression model was fitted to identify the optimum coding algorithm for epilepsy and was internally validated. One hundred fifty-eight out of three hundred (52.6%) epilepsy-coded records and 0/300 (0%) nonepilepsy records were confirmed to have epilepsy. The kappa for interrater agreement was 0.89 (95% CI=0.81-0.97). The model utilizing epilepsy (G40), status epilepticus (G41) and ≥1 antiepileptic drug (AED) conferred the highest positive predictive value of 81.4% (95% CI=73.1-87.9) and a specificity of 99.9% (95% CI=99.9-100.0). The area under the receiver operating curve was 0.90 (95% CI=0.88-0.93). When combined with pharmaceutical data, the precision of case identification for epilepsy data linkage design was considerably improved and could provide considerable potential for efficient and reasonably accurate case ascertainment in epidemiological studies. Copyright © 2015 Elsevier Inc. All rights reserved.
Mudigoudar, Basanagoud; Weatherspoon, Sarah; Wheless, James W
The medical management of the epilepsy syndromes of early childhood (eg, infantile spasms, Dravet syndrome, and Lennox-Gastaut syndrome) is challenging; and requires careful evaluation, classification, and treatment. Pharmacologic therapy continues to be the mainstay of management for these children, and as such it is important for the clinician to be familiar with the role of new antiepileptic drugs. This article reports the clinical trial data and personal experience in treating the severe epilepsies of childhood with the recently Food and Drug Administration-approved new antiepileptic drugs (vigabatrin, rufinamide, perampanel, and clobazam) and those in clinical trials (cannabidiol, stiripentol, and fenfluramine). Genetic research has also identified an increasing number of pediatric developmental and seizure disorders that are possibly treatable with targeted drug therapies, focused on correcting underlying neural dysfunction. We highlight recent genetic advances, and how they affect our treatment of some of the genetic epilepsies, and speculate on the use of targeted genetic treatment (precision medicine) in the future. Copyright © 2016 Elsevier Inc. All rights reserved.
Sisodiya, Sanjay M
Genetic discovery has been extremely rapid over the last year, with many new discoveries illuminating novel mechanisms and pathways. In particular, the application of whole exome and whole genome sequencing has identified many new genetic causes of the epilepsies. As such methods become increasingly available, it will be critical for practicing neurologists to be acquainted with them. This review surveys some important developments over the last year. The range of tests available to the clinician is wide, and likely soon to be dominated by whole exome and whole genome sequencing. Both whole exome and whole genome sequencing have usually proven to be more powerful than most existing tests. Many new genes have been implicated in the epilepsies, with emerging evidence of the involvement of particular multigene pathways. For the practicing clinician, it will be important to appreciate progress in the field, and to prepare for the application of novel genetic testing in clinical practice, as genetic data are likely to contribute importantly for many people with epilepsy.
Sajatovic, Martha; Tatsuoka, Curtis; Welter, Elisabeth; Perzynski, Adam T; Colon-Zimmermann, Kari; Van Doren, Jamie R; Bukach, Ashley; Lawless, Mary Ellen; Ryan, Eleanor R; Sturniolo, Katherine; Lhatoo, Samden
Serious mental illness is disproportionately common in people with epilepsy and contributes to complications and mortality. Few care approaches specifically target individuals who have epilepsy and severe mental illness. We used an iterative process to refine an existing intervention and tested the novel intervention, Targeted Self-Management for Epilepsy and Mental Illness (TIME) in individuals with epilepsy and comorbid mental illness (E-MI). The TIME intervention was developed with input from a community advisory board and then tested for feasibility, acceptability, and preliminary efficacy in people with E-MI, using a 16-week prospective, randomized controlled design comparing TIME (N=22) vs. treatment as usual (TAU, N=22). Primary outcome was change in depressive symptoms, assessed by the Montgomery Asberg Depression Rating Scale (MADRS). Secondary assessments included global psychiatric symptom severity, seizure frequency, sleep patterns, quality of life, stigma, social support, and self-efficacy. There were 44 individuals enrolled, mean age 48.25 (SD=11.82) with 25 (56.8%) African-Americans. The majority (N=31, 70.5%) were unemployed, and most (N=41, 95.5%) had annual income
Garcia-Penas, J J
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.
Steiger, Bettina K; Jokeit, Hennric
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.
Jeong, Anna; Wong, Michael
Epilepsy is one of the most disabling symptoms of tuberous sclerosis complex (TSC) and is a leading cause of morbidity and mortality in affected individuals. The relationship between systemic disease manifestations and the presence of epilepsy has not been thoroughly investigated. This study utilizes a multicenter TSC Natural History Database including 1,816 individuals to test the hypothesis that systemic disease manifestations of TSC are associated with epilepsy. Univariate analysis was used to identify patient characteristics (e.g., age, gender, race, and TSC mutation status) associated with the presence of epilepsy. Individual logistic regression models were built to examine the association between epilepsy and each candidate systemic or neurologic disease variable, controlling for the patient characteristics found to be significant on univariate analysis. Finally, a multivariable logistic regression model was constructed, using the variables found to be significant on the individual analyses as well as the patient characteristics that were significant on univariate analysis. Nearly 88% of our cohort had a history of epilepsy. After adjusting for age, gender, and TSC mutation status, multiple systemic disease manifestations including cardiac rhabdomyomas (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3-3.9, p = 0.002), retinal hamartomas (OR 2.1, CI 1.0-4.3, p = 0.04), renal cysts (OR 2.1, CI 1.3-3.4, p = 0.002), renal angiomyolipomas (OR 3.0, CI 1.8-5.1, p < 0.001), shagreen patches (OR 1.7, CI 1.0-2.7, p = 0.04), and facial angiofibromas (OR 1.7, CI 1.1-2.9, p = 0.03) were associated with a higher likelihood of epilepsy. In the multivariable logistic regression model, cardiac rhabdomyomas (OR 1.9, CI 1.0-3.5, p = 0.04) remained significantly associated with the presence of epilepsy. The identification of systemic disease manifestations such as cardiac rhabdomyomas that confer a higher risk of epilepsy development in TSC could contribute to disease
Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.
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
Electroencephalography (EEG) has an important role in the diagnosis and classification of epilepsy. It can provide information for predicting the response to antiseizure drugs and to identify the surgically remediable epilepsies. In temporal lobe epilepsy (TLE) seizures could originate in the medial or lateral neocortical temporal region, and many of these patients are refractory to medical treatment. However, majority of patients have had excellent results after surgery and this often relies on the EEG and magnetic resonance imaging (MRI) data in presurgical evaluation. If the scalp EEG data is insufficient or discordant, invasive EEG recording with placement of intracranial electrodes could identify the seizure focus prior to surgery. This paper highlights the general information regarding the use of EEG in epilepsy, EEG patterns resembling epileptiform discharges, and the interictal, ictal and postictal findings in mesial temporal lobe epilepsy using scalp and intracranial recordings prior to surgery. The utility of the automated seizure detection and computerized mathematical models for increasing yield of non-invasive localization is discussed. This paper also describes the sensitivity, specificity, and predictive value of EEG for seizure recurrence after withdrawal of medications following seizure freedom with medical and surgical therapy. PMID:22957235
Rossignol, S.; Aregahegn, K. Z.; Ciuraru, R.; Bernard, F.; Tinel, L.; Fine, L.; George, C.
From a few years now, there is a growing body of evidence that photoinduced processes could be of great importance for the tropospheric chemistry. Here, we would like to present two additional outcomes of this new area of research, firstly the photosensitized direct VOC uptake by aerosols and, secondly, the photoinduced chemical formation of unsaturated VOC from marine microlayer proxy. It was recently shown that the chemistry of glyoxal toward ammonium ions into droplets and wet aerosols leads to the formation of light-absorbing compounds. Among them, we found that imidazole-2-carboxaldehyde (IC) acts as a photosensitizer and is able to initiate the growth of organic aerosols via the uptake of VOC, such as limonene. Given its potential importance, the mechanism of this photoinduced uptake was investigated thanks to aerosol flow tube experiments and UPLC-ESI-HRMS analysis. Results reveal hydrogen abstraction on the VOC molecule by the triplet state of IC leading to the VOC oxidation without any traditional oxidant. As well as aerosol, the sea-surface microlayer, known to be enriched in light-absorbing organics, is largely impacted by photochemical processes. Recent studies have pointed out for example the role of photosentitized processes in the loss of NO2 and ozone at water surfaces containing photoactive compounds such as chlorophyll. In order to go further, we worked from sea-surface microlayer proxy containing humic acids as photoactive material and organic acids as surfactants. Beside oxidation processes, we monitored by high resolution PTR-MS the release in the gas phase of unsaturated compounds, including C5 dienes (isoprene ?). A strong correlation between the measured surface tension and the C5 diene concentration in the gas phase was evidenced, clearly pointing toward an interfacial process. This contribution will highlight the similarities between both systems and will attempt to present a general chemical scheme for photosensitized chemistry at
Mauget-Faÿsse, M; Quaranta, M; Francoz, N; BenEzra, D; Mauget-Fa, M
to report on the possible correlation between incident retinal phototoxicity and the use of photosensitizing drugs. four patients were examined because of scotomas and visual loss after an incidental exposure to a strong light source. One patient (two eyes) was exposed to standard camera flash; one patient (one eye) had a brief exposure to welding light; one patient (two eyes) underwent uncomplicated phacoemulsifications with intraocular lens implantation. The fourth patient had a severe retinal phototoxicity following a secondary intraocular lens implantation. All four patients underwent a thorough assessment including history of systemic drug use. These patients had ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts), fundus examination, fluorescein and indocyanine green angiographies and were followed for 1 year. on presentation, the mean visual acuity was 7.5/20 (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal lesions in all affected eyes. Early phase fluorescein angiography showed one or multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window defect. In the late phase, some of these spots leaked the fluorescein dye. Indocyanine green angiography demonstrated hypofluorescent spots throughout with ill-defined borders of hyperfluorescence observed during the late stages. The common finding in these four patients was the fact that they were all taking one or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and benzodiazepines). Three of the patients had a full visual recovery a few months after the phototoxicity. The fourth patient remained with a visual acuity of 20/60 12 months after the light exposure. Despite the visual recovery, non-homogeneous retinal pigment epithelial disturbances persisted in all affected eyes. phototoxicity following incidental light exposure may occur in patients taking drugs of photosensitizing potential. Therefore, the thorough
Zhuang, Xiaoxi; Ma, Xiaowei; Xue, Xiangdong; Jiang, Qiao; Song, Linlin; Dai, Luru; Zhang, Chunqiu; Jin, Shubin; Yang, Keni; Ding, Baoquan; Wang, Paul C; Liang, Xing-Jie
Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.
Wirrell, Elaine C; Grossardt, Brandon R; So, Elson L; Nickels, Katherine C
Purpose To compare long-term outcome in a population-based group of children with cryptogenic vs symptomatic focal epilepsy diagnosed from 1980–2004 and to define the course of epilepsy in the cryptogenic group. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed, non-idiopathic focal epilepsy from 1980–2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long-term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings Of 359 children with newly-diagnosed epilepsy, 215 (60%) had non-idiopathic focal epilepsy. Of these, 206 (96%) were followed for more than 12 months. Ninety five children (46%) were classified as symptomatic. Median follow-up from diagnosis was similar in both groups, being 157 months (25%ile, 75%ile 89, 233) in the cryptogenic group vs 134 months (25%ile, 75%ile 78, 220) in the symptomatic group (p=0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long-term outcome was significantly better in those with cryptogenic vs symptomatic etiology (intractable epilepsy at last follow-up, 7% vs 40%, p<0.001; seizure-freedom at last follow-up, 81% vs 55%, p<0.001). Of those who achieved seizure-freedom at final follow-up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p=0.01). One third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure-free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly
Bonello, M; Michael, B D; Solomon, T
A wide range of infections of the central nervous system are responsible for both acute seizures and epilepsy. The pathogenesis and clinical semiology of the seizure disorders vary widely between the infective pathogens. The exact mechanisms underlying this are poorly understood, but appear, at least in part, to relate to the pathogen; the degree of cortical involvement; delays in treatment; and the host inflammatory response. The treatment of infective causes of seizures involves both symptomatic treatment with antiepileptic drugs and direct treatment of the underlying condition. In many cases, early treatment of the infection may affect the prognosis of the epilepsy syndrome. The greatest burden of acute and long-term infection-related seizures occurs in resource-poor settings, where both clinical and research facilities are often lacking to manage such patients adequately. Nevertheless, education programs may go a long way toward addressing the stigma, leading to improved diagnosis, management, and ultimately to better quality of life. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Wang, Xiaofeng; Luo, Yifeng; Liu, Shuangxi; Tan, Liming; Wang, Sanhu; Man, Rongyong
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
Wasade, Vibhangini S; Spanaki, Marianna; Iyengar, Revathi; Barkley, Gregory L; Schultz, Lonni
Epilepsy Quality Measures (EQM) were developed by the American Academy of Neurology (AAN) to convey standardization and eliminate gaps and variations in the delivery of epilepsy care (Fountain et al., 2011 ). The aim of this study was to identify adherence to these measures and other emerging practice standards in epilepsy care. A 15-item survey was mailed to neurologists in Michigan, USA, inquiring about their practice patterns in relation to EQM. One hundred thirteen of the 792 surveyed Michigan Neurologists responded (14%). The majority (83% to 94%) addressed seizure type and frequency, reviewed EEG and MRI, and provided pregnancy counseling to women of childbearing potential. Our survey identified gaps in practice patterns such as counseling about antiepileptic drug (AED) side effects and knowledge about referral for surgical therapy of intractable epilepsy. Statistical significance in the responses on the AAN EQM was noted in relation to number of years in practice, number of epilepsy patients seen, and additional fellowship training in epilepsy. Practice patterns assessment in relation to other comorbidities revealed that although bone health and sudden unexplained death in epilepsy are addressed mainly in patients at risk, depression is infrequently discussed. The findings in this study indicate that additional educational efforts are needed to increase awareness and to improve quality of epilepsy care at various points of health care delivery. Copyright © 2012 Elsevier Inc. All rights reserved.
Denis, Tyler GSt; Hamblin, Michael R
Photodynamic therapy (PDT) was discovered in 1900 by Raab, and has since emerged as a promising tool for treating diseases characterized by unwanted cells or hyperproliferating tissue (e.g., cancer or infectious disease). PDT consists of the light excitation of a photosensitizer (PS) in the presence of O2 to yield highly reactive oxygen species. In recent years, PDT has been improved by the synthesis of targeted bioconjugates between monoclonal antibodies and PS, and by investigating PS biodistribution and PD. Here, we provide a comprehensive review of major developments in PS-immunoconjugate-based PDT and the bioanalysis of these agents, with a specific emphasis on anticancer and antimicrobial PDT. PMID:23641699
Trotter, D. M., Jr.; Smith, D. W.
A new effect which allows direct formation of thin metal films of controlled morphology is described. Patterns of glass-ceramic opal are developed in photosensitive glass samples by UV irradiation and heat treatment. The samples are then ion exchanged in molten salt baths containing Ag+ or Cu+ ions. On subsequent firing in a hydrogen atmosphere, continuous films with typical thin metal films properties grow on the opal regions of the samples. Discontinuous films, characterized by activated resistivities and switching, grow on the glassy regions.
Nag, Okhil K.; Naciri, Jawad; Delehanty, James B.
The main principle of photodynamic therapy (PDT) is to kill malignant cells by generation of reactive oxygen species (ROS). PDT appeared highly effective when ROS can be produced in subcellular location such as plasma membrane. The plasma membrane maintains the structural integrity of the cell and regulates multiple important cellular processes, such as endocytosis, trafficking, and apoptotic pathways, could be one of the best points to kill the cancer cells. Previously, we have developed a plasma membrane-targeted liquid crystal nanoparticle (LCNP) formulation that can be loaded with dyes or drugs. Here we highlight the utility of this LCNP for membrane targeted delivery and imaging for a photosensitizer (PS) for PDT applications.
O'Toole, Stephanie; Lambert, Veronica; Gallagher, Pamela; Shahwan, Amre; Austin, Joan K
The aim of this qualitative study was to explore the challenges that parents of children with epilepsy experienced when engaging in dialog with their child about epilepsy and epilepsy-related issues. Using a qualitative exploratory approach, interviews were conducted with 34 parents of children with epilepsy (aged 6-16 years), consisting of 27 mothers and 7 fathers. Data were transcribed verbatim and thematically analyzed. Findings revealed five main themes: normalizing epilepsy, the invisibility of epilepsy, information concealment, fear of misinforming the child, and difficulty in discussing particular epilepsy-related issues. Many of the communicative challenges experienced by parents impacted on their ability to engage openly in parent-child dialog about epilepsy in the home. Parents face specific challenges when choosing to communicate with their child about epilepsy, relating to creating a sense of normality, reducing fear of causing their child worry, and having a lack of epilepsy-related knowledge. Healthcare professionals who work closely with families living with epilepsy should remain mindful of the importance of discussing family communication surrounding epilepsy and the challenges parents of children with epilepsy face when talking about epilepsy within the home. Copyright © 2016 Elsevier Inc. All rights reserved.
Epilepsy and the "falling sickness" are mentioned three times in Shakespeare, in Julius Caesar, I.ii, Othello, IV.i., and figuratively in King Lear, II.ii. The present article surveys these passages in the context of modern research findings, literary as well as medico-historical. It adds further material from Renaissance texts and concludes that epilepsy is an omnibus term for a variety of symptoms and pathological conditions, and that Shakespeare's idea of epilepsy is closer to popular stereotypes than has hitherto been assumed.
Laskowska, M; Leszczyńska-Gorzelak, B; Oleszczuk, J
The aim of this study was to analyze the outcome of pregnancy and delivery in epileptic women. A retrospective review of the 41 pregnant women with epilepsy who delivered in the Department of Obstetrics and Perinatology of the University School of Medicine in Lublin over 7 years (1993-1999) was carried out. Women with epilepsy had more pregnancy complications including premature labor, anemia, hypertension, vaginal bleeding, urinary tract infection, nausea and vomiting. An increased risk of congenital malformations and intrauterine fetal growth retardation was observed. Women with epilepsy require more extensive pregnancy planning including neurologic and preconceptional care. Copyright 2001 S. Karger AG, Basel.
Sorge, Shawn T; Hesdorffer, Dale C; Phelan, Jo C; Winawer, Melodie R; Shostak, Sara; Goldsmith, Jeff; Chung, Wendy K; Ottman, Ruth
Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients' psychological responses and coping strategies, but little is known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that among members of families containing multiple individuals with epilepsy, depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause. A self-administered survey was completed by 417 individuals in 104 families averaging 4 individuals with epilepsy per family. Current depression was measured with the Patient Health Questionnaire. Genetic causal attribution was assessed by three questions addressing the following: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual's epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biologic relatives without epilepsy, and 3.9% in 51 individuals married into the families. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biologic relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p = 0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in families containing
Prontera, P; Sarchielli, P; Caproni, S; Bedetti, C; Cupini, L M; Calabresi, P; Costa, C
Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.
Edelvik, Anna; Rydenhag, Bertil; Olsson, Ingrid; Flink, Roland; Kumlien, Eva; Källén, Kristina
Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten- and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified ≥30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients. PMID:23966252
Suppiej, Agnese; Mastrangelo, Massimo; Mastella, Laura; Accorsi, Patrizia; Grazian, Luisa; Casara, Gianluca; Peruzzi, Cinzia; Carpanelli, Maria Luisa; Janes, Augusta; Traverso, Annalisa; Dalla Bernardina, Bernardo
Neonatal seizures are a risk factor for later epilepsy and their etiology is known to be implicated in the outcome but, little is known about this issue in the subgroup of seizures symptomatic of perinatal arterial ischemic stroke. The aim of this study was to describe the long term risk of epilepsy after electroencephalographic confirmed neonatal seizures symptomatic of perinatal arterial ischemic stroke. Fifty-five patients with electroclinical ictal data, vascular territory confirmed by neuroimaging and a minimum follow up of 3.5 years were identified from a multi-centre prospective neonatal seizures registry. Primary outcome was occurrence of post-neonatal epilepsy. The association of outcome with family history of epilepsy, gender, location of the infarct, neonatal clinical and electroencephalogram data were also studied. During a mean follow up of 8 years and 5 months, 16.4% of the patients developed post neonatal epilepsy. The mean age at first post neonatal seizure was 4 years and 2 months (range 1-10 years and 6 months). Location of the infarct was the only statistically significant risk factor (p=0.001); epilepsy was more represented in males but the difference was not statistically significant. Neonatal seizures symptomatic of perinatal arterial ischemic stroke had lower risk and later onset of post-neonatal epilepsy, compared to seizures described in the setting of other perinatal brain insults. Our data have implications for counseling to the family at discharge from neonatal intensive care unit. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Abulhamail, Albaraa S; Al-Sulami, Fahad E; Alnouri, Mouneeb A; Mahrous, Najeeb M; Joharji, Dima G; Albogami, Maha M; Jan, Mohammed M
Primary school teacher's knowledge and attitudes toward epilepsy can have significant impact on the performance and psycho-social development of the child with epilepsy. Our objectives were to study teacher's knowledge and attitudes and identify areas in which further teacher training and education are required. A stratified random sample survey involving a group of primary school teachers in Jeddah, Saudi Arabia included private/public schools designated for male and female students. A structured 37-item questionnaire was used to examine their demographics, knowledge, attitudes, and experience with epilepsy. Six hundred and twenty primary school teachers working in public (58%) or private (42%) schools were included with ages ranging between 21 and 59 years (mean 36). Most teachers (79%) were of Saudi Arabian nationality and 66% had a college or university degree. Their years of experience ranged from 1 to 35 (mean 13.5). Only 17% of the teachers felt very well informed about epilepsy. Teachers with higher education were more likely to have good knowledge (p=0.009). Teachers of Saudi nationality were also more likely to report good knowledge, independent of their educational level (p=0.013). Overall, teachers with good knowledge were less likely to have negative attitudes including minding to have an epileptic child in their class (p=0.028) or thinking that they should be placed in a special classroom (p=0.029). Primary school teacher's knowledge about epilepsy needs improvements. Their attitudes correlated highly with their knowledge. Educational campaigns about epilepsy are needed to develop a well informed and tolerant community. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Packer, Rowena M A; McGreevy, Paul D; Salvin, Hannah E; Valenzuela, Michael J; Chaplin, Chloe M; Volk, Holger A
Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.
McGreevy, Paul D.; Salvin, Hannah E.; Valenzuela, Michael J.; Chaplin, Chloe M.; Volk, Holger A.
Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments. PMID:29420639
Ogunrin, Olubunmi A; Adeyekun, Ademola; Adudu, Philomena
The understanding of causation of epilepsy, especially in resource poor African countries where prevalence rates are very high, would aid strategies for primary prevention. This study sought to determine the causes of epilepsy in Nigerian Africans and health-itinerary of patients with epilepsy. This was an observational, cross-sectional descriptive study of consecutive newly diagnosed adult patients with epilepsy using a mixed-methods approach of face-to-face in-depth interview of patients' parents and relations, health care personnel who had given medical attention at any time and telephone interview. A structured interview schedule was used to obtain demographic information, details of seizure variables, health seeking itinerary and history of previous hospitalizations. Data was analyzed descriptively with SPSS version 17. Three hundred and forty-two patients with epilepsy with a mean age of 31.4±11.98 years participated in the study. Most of the patients (68.1%; 233/342) were unemployed and students. There were 270 (78.9%) patients with generalized epilepsy. No identifiable etiology was found in 37.7%, but of the remaining 62.3%, the commonest causes included post traumatic (19.6%), recurrent childhood febrile convulsions (13.2%), post-stroke (6.7%), brain tumors (5.9%), neonatal jaundice (5.3%), birth-related asphyxia (5%) and history of previous CNS infections (4.7%). Family history of epilepsy was obtained in 9.9%, all of whom had primarily generalized seizures. 61.4% of them sought initial attention from the traditional healers or in prayer houses. This study showed the pattern of causes of epilepsy in Nigerian Africans. The health seeking behavior and itinerary of the PWE revealed a preference for traditional healers. There is need for health policies and epilepsy awareness campaigns to prevent causes of seizures and improve the knowledge of the public respectively. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights
Michaelis, Rosa; Tang, Venus; Goldstein, Laura H; Reuber, Markus; LaFrance, William Curt; Lundgren, Tobias; Modi, Avani C; Wagner, Janelle L
Given the significant impact that psychosocial factors and epilepsy treatments can have on the health-related quality of life (HRQOL) of individuals with epilepsy and their families, there is great clinical interest in the role of psychological evaluation and treatments to improve HRQOL and comorbidities. Therefore, the International League Against Epilepsy (ILAE) charged the Psychology Task Force with the development of recommendations for clinical care based on evaluation of the evidence from their recent Cochrane review of psychological treatments in individuals with epilepsy. The literature search for a recent Cochrane review of randomized controlled trials investigating psychological treatments for individuals with epilepsy constitutes the key source of evidence for this article. To provide practical guidance to service providers, we provide ratings on study research designs based on (1) the American Academy of Neurology's Level of Evidence system and (2) the Grading of Recommendations, Assessment, Development, and Evaluation system. This paper is the culmination of an international collaboration process involving pediatric and adult psychologists, neurologists, psychiatrists, and neuropsychiatrists. The process and conclusions were reviewed and approved by the ILAE Executive Committee. The strongest evidence for psychological interventions was identified for the most common mental health problems, including depression, neurocognitive disturbances, and medication adherence. Psychological interventions targeting the enhancement of HRQOL and adherence and a decrease in comorbidity symptoms (anxiety, depression) should be incorporated into comprehensive epilepsy care. There is a range of psychological strategies (ie, cognitive behavioral therapy and mindfulness-based therapies) that show promise for improving the lives of persons with epilepsy, and clinical recommendations are provided to assist epilepsy health care providers in treating the comorbidities and
Özdemir, Osman; Cilingir, Vedat; Özdemir, Pınar Güzel; Milanlioglu, Aysel; Hamamci, Mehmet; Yilmaz, Ekrem
A few studies have explored dissociative experiences in epilepsy patients. We investigated dissociative experiences in patients with epilepsy using the dissociative experiences scale (DES). Ninety-eight patients with epilepsy and sixty healthy controls were enrolled in this study. A sociodemographic questionnaire and the Dissociative Experiences Scale (DES), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered to the participants. The DES scores were significantly higher for the patients with epilepsy than the healthy individuals. The number of individuals with pathological dissociation (DES ≥ 30) was higher in the epilepsy group (n = 28) than in the control group (n = 8). Also, higher levels of dissociation were significantly associated with frequency of seizures, but were not associated with duration of epilepsy and age at onset of the disorder. These findings demonstrate that patients with epilepsy are more prone to dissociation than controls. The high rate of dissociative experiences among patients with epilepsy suggest that some epilepsy-related factors are present.
Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna
Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890
Peercy, P.S.; Land, C.E.
The photosensitivity of lead lanthanum zirconate titanate (PLZT) ceramic material used in high resolution, high contrast, and non-volatile photoferroelectric image storage and display devices is enhanced significantly by positive ion implantation of the PLZT near its surface. Ions that are implanted include H/sup +/, He/sup +/, Ar/sup +/, and a preferred co-implant of Ar/sup +/ and Ne/sup +/. The positive ion implantation advantageously serves to shift the band gap energy threshold of the PLZT material from near-uv light to visible blue light. As a result, photosensitivity enhancement is such that the positive ion implanted PLZT plate is sensitive even to sunlight and conventional room lighting, such as fluorescent and incandescent light sources. The method disclosed includes exposing the PLZT plate to these positive ions of sufficient density and with sufficient energy to provide an image. The PLZT material may have a lanthanum content ranging from 5 to 10%; a lead zirconate content ranging from 62 to 70 mole %; and a lead titanate content ranging from 38 to 30%. The region of ion implantation is in a range from 0.1 to 2 microns below the surface of the PLZT plate. Density of ions is in the range from 1 x 10/sup 12/ to 1 x 10/sup 17/ ions/cm/sup 2/ and having an energy in the range from 100 to 500 keV.
Skliutas, Edvinas; Kasetaite, Sigita; Jonušauskas, Linas; Ostrauskaite, Jolita; Malinauskas, Mangirdas
Recent advances in material engineering have shown that renewable raw materials, such as plant oils or glycerol, can be applied for synthesis of polymers due to ready availability, inherent biodegradability, limited toxicity, and existence of modifiable functional groups and eventually resulting to a potentially lower cost. After additional chemical modifications (epoxidation, acrylation, double bonds metathesis, etc.), they can be applied in such high-tech areas as stereolithography, which allows fabrication of three-dimensional (3-D) objects. "Autodesk's" 3-D optical printer "Ember" using 405-nm light was implemented for dynamic projection lithography. It enabled straightforward spatio-selective photopolymerization on demand, which allows development of various photosensitive materials. The bio-based resins' photosensitivity was compared to standard "Autodesk" "PR48" and "Formlabs" "Clear" materials. It turned out that the bioresins need a higher energy dose to be cured (a least 16 J · cm - 2 for a single layer varying from 100 to 130 μm). Despite this, submillimeter range 2.5-D structural features were formed, and their morphology was assessed by optical profilometer and scanning electron microscope. It was revealed that a higher exposition dose (up to 26 J · cm - 2) results in a linear increase in the formed structures height, proving controllability of the undergoing process. Overall, the provided results show that naturally derived resins are suitable candidates for tabletop gray-tone lithography.
Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba
Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.
Souza, Paulo E C; Oliveira, Samuel S; Aguiar-Filho, Cristiano R; Cunha, Ana L B; Albuquerque, Raquel F; Evêncio-Neto, Joaquim; Riet-Correa, Franklin; Mendonça, Fábio S
Three outbreaks of primary photosensitization caused by Froelichia humboldtiana are reported in the semiarid region of the states of Pernambuco and Paraíba, in northeastern Brazil. The disease occurred from March to June 2011, affecting 27 bovines out of a total of 70. The main lesions consisted of dermatitis of the white skin, with edema and necrosis. All the bovines recovered after removal from the areas invaded by F. humboldtiana. To produce the disease experimentally, one bovine with white skin was placed for 14 days into an area with F. humboldtiana as the sole forage. This bovine presented photodermatitis on the third day of consumption. The serum concentrations of total, indirect, and conjugated bilirubin and the serum activities of gamma-glutamyl transferase (GGT) and aspartate-aminotransferase (AST) in the spontaneously affected cattle and in the experimental cattle remained within normal ranges. It is concluded that F. humboldtiana causes primary photosensitization in cattle in northeastern Brazil. Copyright © 2012 Elsevier Ltd. All rights reserved.
Romano, Renan A; Pratavieira, Sebastião; Silva, Ana P da; Kurachi, Cristina; Guimarães, Francisco E G
Photodynamic Inactivation (PDI) is based on the use of a photosensitizer (PS) and light that results mainly in the production of reactive oxygen species, aiming to produce microorganism cell death. PS incubation time and light dose are key protocol parameters that influence PDI response; the correct choice of them can increase the efficiency of inactivation. The results of this study show that a minor change in the PDI protocol, namely light-driven incubation leads to a higher photosensitizer and more uniform cell uptake inside the irradiated zone. Furthermore, as the uptake increases, the damage caused by PDI also increases. The proposed light-driven incubation prior to the inactivation illumination dose has advantages when compared to the traditional PDI treatments since it can be more selective and effective. Using a violet light as pre-illumination (light-driven incubation) source and a red-light system as PDI source, it was possible to demonstrate that when compared to the traditional protocol of dark incubation, the pre-illuminated cell culture showed an inactivation increase of 7 log units. These in vitro results performed in Candida albicans cells may result in the introduction of a new protocol for PDI. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
... evidence-based strategies to achieve the legislative purpose of the program. As a result of the evaluation... newly published Institute of Medicine recommendations for the Epilepsies, focusing on evaluating...
Keangpraphun, T; Towanabut, S; Chinvarun, Y; Kijsanayotin, P
One-third of patients with epilepsy are resistant to anti-epileptic drugs (AEDs). Drug-resistant epilepsy is believed to be multifactorial involving both genetic and non-genetic factors. Genetic variations in the ABCB1 gene encoding the drug efflux transporter, p-glycoprotein (p-gp), may influence the interindividual variability in AED response by limiting drugs from reaching their target. Phenobarbital (PB), one of the most cost-effective and widely used AEDs in developing countries, has been reported to be transported by p-gp. This study aimed to investigate the association of a genetic variant, ABCB1 3435C>T, and non-genetic factors with phenobarbital response in Thai patients with epilepsy. One hundred and ten Thai patients with epilepsy who were treated with PB maintenance doses were enrolled in this study. Two phenotypic groups, PB-responsive epilepsy and PB-resistant epilepsy, were defined according to the International League Against Epilepsy (ILAE) criteria. Subjects were genotyped for ABCB1 3435C>T (rs1045642). Multiple logistic regression analysis was tested for the association of ABCB1 3435C>T polymorphism and non-genetic factors with PB response. Sixty-two PB-responsive epilepsy subjects and 48 PB-resistant epilepsy subjects were identified. All genotype frequencies of the ABCB1 3435C>T SNP were consistent with the Hardy-Weinberg equilibrium (P > 0·05). The ABCB1 3435C>T polymorphism and type of epilepsy were associated with response to PB. Patients with PB-resistant epilepsy had a significantly higher frequency of ABCB1 3435CC genotype and had focal epilepsy more often than patients with PB-responsive epilepsy (adjusted OR = 3·962, 95% CI = 1·075-14·610, P-value = 0·039; adjusted OR = 5·936, 95% CI = 2·272-15·513, P-value < 0·001, respectively). The model explained 25·5% of the variability in response to PB (R(2) = 0·255). Thai patients of ABCB1 3435CC genotype and with focal epilepsy were more often PB resistant. Those two
Belik, V. P.; Beltukova, D. M.; Gadzhiev, I. M.; Semenova, I. V.; Vasyutinskii, O. S.
The luminescence spectrum of aqueous solution of Radachlorin photosensitizer in the near IR spectral range (950-1350 nm) has been determined at the excitation in both the Soret and Q absorption bands. Major sources of the recorded luminescence were analyzed. Kinetics of photosensitizer and singlet oxygen phosphorescence signals were studied by means of time-resolved spectroscopy. The corresponding characteristic lifetimes were determined.
Klimenko, V. V.; Shmakov, S. V.; Kaydanov, N. E.; Knyazev, N. A.; Kazakov, N. V.; Rusanov, A. A.; Bogdanov, A. A.; Dubina, M. V.
In this present study we investigate the Radachlorin photosensitizer accumulation in K562 cells and Hela cells and determined the cell viability after PDT. Using the macroscopic singlet oxygen modeling and cellular photosensitizer concentration the singlet oxygen threshold doses for K562 cells and Hela cells were calculated.
Ramaprasad, Subbaraya; Liu, Y. H.; Pandey, R. K.; Shiau, Fuu-Yau; Smith, Kevin M.
Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of cancer. We are using newly synthesized and chemically defined and characterized porphyrin photosensitizers that are specifically labeled with deuterium to perform in vivo NMR studies in a murine tumor model. In vivo magnetic resonance offers the potential for repetitive, safe, noninvasive evaluation of photosensitizers, tumor metabolism, and the effect of PDT on the tumor metabolism. In an effort to monitor noninvasively the photosensitizers in an in vivo tumor model, we are synthesizing several deuterium labeled photosensitizers which absorb red light at or above 630 nm. Development of methods to test these photosensitizers directly in humans is not feasible at this time, since these photosensitizers are new and we do not yet understand the side effects. In addition, we do not understand the potential benefits compared with Photofrin II, the widely used photosensitizer. To perform our in vivo deuterium NMR studies on mouse foot tumors, we have constructed a solenoid coil which operates at 30.7 MHz for the deuterium nucleus. We have been able to detect the deuterium labeled photosensitizer in the tumor after a direct intra-tumor injection. The use of 31P NMR to predict the possible outcome of PDT in these tumors is also discussed.
Jing, Bingwen; Zhang, Manhua; Shen, Tao
[structure: see text] A dyad of eosin and tris(2,2'-bipyridine)Ru(II) was prepared, and its photophysical properties were investigated. The photosensitization of eosin is greatly enhanced by introduction of tris(2,2'-bipyridine)Ru(II), which is verified via photooxygenation of anthracene derivatives. The electron-transfer mechanism of photosensitization is also discussed.
Sorge, Shawn T.; Hesdorffer, Dale C.; Phelan, Jo C.; Winawer, Melodie R.; Shostak, Sara; Goldsmith, Jeff; Chung, Wendy K.; Ottman, Ruth
Summary Objectives Rapid advances in genetic research and increased use of genetic testing have increased the emphasis on genetic causes of epilepsy in patient encounters. Research in other disorders suggests that genetic causal attributions can influence patients’ psychological responses and coping strategies, but little is currently known about how epilepsy patients and their relatives will respond to genetic attributions of epilepsy. We investigated the possibility that depression, the most frequent psychiatric comorbidity in the epilepsies, might be related to the perception that epilepsy has a genetic cause among members of families containing multiple individuals with epilepsy. Methods A self-administered survey was completed by 417 individuals in 104 families averaging four individuals with epilepsy per family. Current depression was measured with the PHQ-9. Genetic causal attribution was assessed by three questions addressing: perceived likelihood of having an epilepsy-related mutation, perceived role of genetics in causing epilepsy in the family, and (in individuals with epilepsy) perceived influence of genetics in causing the individual’s epilepsy. Relatives without epilepsy were asked about their perceived chance of developing epilepsy in the future, compared with the average person. Results Prevalence of current depression was 14.8% in 182 individuals with epilepsy, 6.5% in 184 biological relatives without epilepsy, and 3.9% in 51 married-in individuals. Among individuals with epilepsy, depression was unrelated to genetic attribution. Among biological relatives without epilepsy, however, prevalence of depression increased with increasing perceived chance of having an epilepsy-related mutation (p=0.02). This association was not mediated by perceived future epilepsy risk among relatives without epilepsy. Significance Depression is associated with perceived likelihood of carrying an epilepsy-related mutation among individuals without epilepsy in
Bianchin, Marino Muxfeldt; Londero, Renata Gomes; Lima, José Eduardo; Bigal, Marcelo Eduardo
The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.
Ferraro, Thomas N
Genetic analysis is providing new information on the biological basis of epilepsy at a rapid pace; this article identifies factors acting as major barriers to use of these data for therapy development. Disease heterogeneity is a primary obstacle since so many genes can cause or predispose to epilepsy and the clinical presentation of epilepsy is so diverse, thus making it difficult to define the most therapeutically relevant targets. Further, many epilepsy genes affect brain development, an observation that represents a barrier unto itself given the challenge of reversing or preventing genetically mediated alterations of brain pathway formation. Finally, the lack of appropriate models for testing new therapies is also recognized as a fundamental limitation. Overcoming these barriers will be aided by full characterization of the genetic landscape of epilepsy, elucidation of key pathway points for therapeutic intervention and creation of unique experimental models to validate results.
Besag, Frank; Ettinger, Alan B.; Mula, Marco; Gobbi, Gabriella; Comai, Stefano; Aldenkamp, Albert P.; Steinhoff, Bernhard J.
Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID:27255267
Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M
A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Epilepsy-associated stigma in Bolivia: a community-based study among the Guarani population: an International League Against Epilepsy/International Bureau for Epilepsy/World Health Organization Global Campaign Against Epilepsy Regional Project.
Bruno, Elisa; Bartoloni, Alessandro; Sofia, Vito; Rafael, Florentina; Magnelli, Donata; Padilla, Sandra; Quattrocchi, Graziella; Bartalesi, Filippo; Segundo, Higinio; Zappia, Mario; Preux, Pierre-Marie; Nicoletti, Alessandra
Epilepsy is associated with a significant burden of social stigma that appears to be influenced by psychosocial and cultural factors. Stigma has a negative effect on the management of people with epilepsy (PWE), representing one of the major factors that contribute to the burden of epilepsy. To assess stigma perception among the Guarani population, one hundred thirty-two people living in Guaraní communities in Bolivia were invited to complete the Stigma Scale of Epilepsy questionnaire. The main determinants of stigma identified were: the fear linked to loss of control, the feelings of sadness and pity toward PWE, the difficulties faced by PWE in the professional and relationship fields, the level of education and type of seizure. Our study pointed out that, in this population, PWE face difficulties in everyday life because of epilepsy-associated stigma and the results attest to the importance of promoting community-based educational programs aimed at reducing the stigmatization process. Copyright © 2012 Elsevier Inc. All rights reserved.
Modi, Avani C; Wagner, Janelle; Smith, Aimee W; Kellermann, Tanja S; Michaelis, Rosa
The International League Against Epilepsy (ILAE) Neuropsychiatry commission and United States Institute of Medicine report both identified cognitive and psychological comorbidities as a significant issue for individuals with epilepsy, with rates as high as 60%. However, there is a paucity of evidence-based treatments for many psychological conditions (e.g., learning disorders, cognitive disorders, behavioral disorders). Because of inherent challenges in the implementation of psychological therapy trials and specific considerations for the population with epilepsy, the focus of the current review was to provide guidance and recommendations to conduct psychological trials for individuals with epilepsy. Several key areas will be discussed, including selection of patients, trial design, psychological intervention considerations, outcomes and evaluation of results, publication of trial results, and special issues related to pediatric clinical trials. Rigorously designed psychological therapy trials will set the stage for evidence-based practice in the care of individuals with epilepsy, with the goal of improving seizures, side effects, and HRQOL. Copyright © 2017 Elsevier Inc. All rights reserved.
Yan, Song; Wu, Yuanbin; Deng, Yanchun; Liu, Yonghong; Zhao, Jingjing; Ma, Lei
Fatigue is highly prevalent in patients with epilepsy and has a major impact on quality of life, but little data is available on its effects and management in epilepsy. To identify the incidence and risk factors of fatigue in patients with epilepsy, 105 epilepsy patients (45 women and 60 men) were enrolled in our study. Demographic and clinical data were collected and psychological variables including fatigue, sleep quality, excess daytime sleepiness, anxiety, and depression were measured by Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale, respectively. Of 105 patients, 29.5% exhibited fatigue (FSS score ⩾4). We found no correlation between the occurrence of fatigue and any of our demographic or clinical variables. Fatigue is correlated with low sleep quality, anxiety, and depression, but not with excess daytime sleepiness. Thus, we concluded that fatigue is highly prevalent in patients with epilepsy, and that low sleep quality, anxiety, and depression are significantly correlated with fatigue in epileptics, while excess daytime sleepiness not. Copyright © 2016. Published by Elsevier Ltd.
Meyer, Ana-Claire; Dua, Tarun; Ma, Juliana; Saxena, Shekhar; Birbeck, Gretchen
To describe the magnitude and variation of the epilepsy treatment gap worldwide. We conducted a systematic review of the peer-reviewed literature published from 1 January 1987 to 1 September 2007 in all languages using PubMed and EMBASE. The purpose was to identify population-based studies of epilepsy prevalence that reported the epilepsy treatment gap, defined as the proportion of people with epilepsy who require but do not receive treatment. Negative binomial regression models were used to assess trends and associations. The treatment gap was over 75% in low-income countries and over 50% in most lower middle- and upper middle-income countries, while many high-income countries had gaps of less than 10%. However, treatment gaps varied widely both between and within countries. They were significantly higher in rural areas (rate ratio, RR: 2.01; 95% confidence interval, CI: 1.40-2.89) and countries with lower World Bank income classification (RR: 1.55; 95% CI: 1.32-1.82). There was no significant trend in treatment gap over time (RR: 0.92; 95% CI: 0.79-1.07). There is dramatic global disparity in the care for epilepsy between high- and low- income countries, and between rural and urban settings. Our understanding of the factors affecting the treatment gap is limited; future investigations should explore other potential explanations of the gap.
Dua, Tarun; Ma, Juliana; Saxena, Shekhar; Birbeck, Gretchen
Abstract Objective To describe the magnitude and variation of the epilepsy treatment gap worldwide. Methods We conducted a systematic review of the peer-reviewed literature published from 1 January 1987 to 1 September 2007 in all languages using PubMed and EMBASE. The purpose was to identify population-based studies of epilepsy prevalence that reported the epilepsy treatment gap, defined as the proportion of people with epilepsy who require but do not receive treatment. Negative binomial regression models were used to assess trends and associations. Findings The treatment gap was over 75% in low-income countries and over 50% in most lower middle- and upper middle-income countries, while many high-income countries had gaps of less than 10%. However, treatment gaps varied widely both between and within countries. They were significantly higher in rural areas (rate ratio, RR: 2.01; 95% confidence interval, CI: 1.40–2.89) and countries with lower World Bank income classification (RR: 1.55; 95% CI: 1.32–1.82). There was no significant trend in treatment gap over time (RR: 0.92; 95% CI: 0.79–1.07). Conclusion There is dramatic global disparity in the care for epilepsy between high- and low- income countries, and between rural and urban settings. Our understanding of the factors affecting the treatment gap is limited; future investigations should explore other potential explanations of the gap. PMID:20431789
Shon, Young Min; Joung, Woo Joung
The purpose of this study was to understand and describe the illness experience of married Korean women with epilepsy. Data were collected during 2015~2016 through individual in-depth interviews with 12 married women with epilepsy. Verbatim transcripts were analyzed using Giorgi's phenomenological analysis to uncover the meaning of the illness experience of the participants. The study results showed that the illness experience of married Korean women with epilepsy was clustered into a specific description of situated structure and a general description of situated structure. Six themes from 20 meaning units were identified: 1) Undermined self-esteem with stigma of being epileptic; 2) Limited social interaction; 3) Suffering sorrow as a 'disqualified being'; 4) Shuttling back and forth across the boundary between healthy and epileptic; 5) Desperate struggle to meet the expectation of given role; 6) Self-empowering through self-restriction and realization. The findings from this study show that both the enacted and felt stigma of epilepsy impact on the life of married Korean women with epilepsy. Although the participants face social and interpersonal restriction and prejudices, they try their best to fulfill their role rather than to be cared for as patients. As the stigma and hardships of the participants are related to lack of knowledge, health professionals should focus not just on clinical intervention but also on providing targeted educational programs and counseling for these women to dispel the stigma of the disease and to increase their quality of life. © 2017 Korean Society of Nursing Science
Epilepsy is a common disease worldwide causing significant physical and social disability. It is one of the most treatable neurological diseases. Yet, in rural, poorer countries like much of India and Nepal, most people with epilepsy are not undergoing any treatment often because they cannot access doctors. Conventional Approaches: It is being appreciated that perhaps doctors are not the solution and that enabling health workers to treat epilepsy may be better. Few details, however, have been put forward about how that might be achieved. Thinking Differently: Untreated epilepsy should be considered a public health problem like HIV/AIDS, the various steps needed for treatment identified and solutions found. Telemedicine Approaches: Telemedicine might contribute to two steps - diagnosis and review. A tool that enables non-doctors to diagnose episodes as epileptic has been developed as a mobile phone app and has good applicability, sensitivity, and specificity for the diagnosis. There are a number of ways in which the use of phone review or short messaging service can improve management. Telemedicine, as part of a public health program, can potentially help the millions of people in the resource-poor world with untreated epilepsy.