Seizure is the most common paediatric neurological disorder, with up to 10% of children having at least one attack of seizures during childhood. Despite the great expansion of seizure treatments in children in the recent years, many patients are refractory to medical treatment. The discovery of microRNAs (miRNAs) revolutionized the world of molecular biology. Extensive studies have suggested crucial roles for miRNAs in human biology of health and disease. Recently, miRNAs proved to be important players in understanding the pathogenesis of epilepsy and seizure disorders. MiRNAs have furthermore emerged as promising therapeutic targets for multiple neurological and non-neurological disorders. MiR-9 is a brain-enriched miRNA which plays an important role in brain development and is found to be upregulated in an immature rat model with seizures and also in children and adults with epilepsy. Therefore, we postulate that miR-9 might be a potential molecular therapeutic target for anti-convulsant therapy in the developing brains.
{"title":"Could silencing of brain-enriched miR-9 reduce seizures in drug resistant epileptic developing brains?","authors":"Ahmed G. Omran, Dalia Elimam","doi":"10.14800/MCE.219","DOIUrl":"https://doi.org/10.14800/MCE.219","url":null,"abstract":"Seizure is the most common paediatric neurological disorder, with up to 10% of children having at least one attack of seizures during childhood. Despite the great expansion of seizure treatments in children in the recent years, many patients are refractory to medical treatment. The discovery of microRNAs (miRNAs) revolutionized the world of molecular biology. Extensive studies have suggested crucial roles for miRNAs in human biology of health and disease. Recently, miRNAs proved to be important players in understanding the pathogenesis of epilepsy and seizure disorders. MiRNAs have furthermore emerged as promising therapeutic targets for multiple neurological and non-neurological disorders. MiR-9 is a brain-enriched miRNA which plays an important role in brain development and is found to be upregulated in an immature rat model with seizures and also in children and adults with epilepsy. Therefore, we postulate that miR-9 might be a potential molecular therapeutic target for anti-convulsant therapy in the developing brains.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81981439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Scorza, R. Cysneiros, A. Almeida, A. M. Rodrigues, E. Cavalheiro, F. Scorza
Background: Schizophrenia is not a single disease entity once it has multiple etiological factors and pathophysiological mechanisms but common phenotypic features. Furthermore, it is associated with increased mortality and reduced life expectancy, with cardiovascular disease being the most common cause of death. People with schizophrenia are at high risk of metabolic syndrome once some antipsychotics drugs frequently cause weight gain, dyslipidemia and diabetes mellitus and these facts together are important risk factors for cardiovascular diseases and even to the occurrence of sudden death in this specific population. Discussion: The long-term effects of metabolic syndrome on overall mortality and cardiovascular mortality is a fact that should not be neglected among individuals com schizophrenia. We debate that supplementation with omega-3 fatty acids is extremely beneficial for people with schizophrenia, since it is clearly demonstrated that this polyunsaturated fatty acid has a positive action in both the metabolic syndrome as in cardiovascular dysfunctions. Summary: We suggest that omega-3 supplementation must be considered in the treatment of people with schizophrenia aiming at reducing risk factor for sudden unexpected death.
{"title":"When the clock stops ticking, metabolic syndrome explodes. Does omega-3 is able to disarm this bomb?","authors":"C. Scorza, R. Cysneiros, A. Almeida, A. M. Rodrigues, E. Cavalheiro, F. Scorza","doi":"10.14800/MCE.105","DOIUrl":"https://doi.org/10.14800/MCE.105","url":null,"abstract":"Background: Schizophrenia is not a single disease entity once it has multiple etiological factors and pathophysiological mechanisms but common phenotypic features. Furthermore, it is associated with increased mortality and reduced life expectancy, with cardiovascular disease being the most common cause of death. People with schizophrenia are at high risk of metabolic syndrome once some antipsychotics drugs frequently cause weight gain, dyslipidemia and diabetes mellitus and these facts together are important risk factors for cardiovascular diseases and even to the occurrence of sudden death in this specific population. Discussion: The long-term effects of metabolic syndrome on overall mortality and cardiovascular mortality is a fact that should not be neglected among individuals com schizophrenia. We debate that supplementation with omega-3 fatty acids is extremely beneficial for people with schizophrenia, since it is clearly demonstrated that this polyunsaturated fatty acid has a positive action in both the metabolic syndrome as in cardiovascular dysfunctions. Summary: We suggest that omega-3 supplementation must be considered in the treatment of people with schizophrenia aiming at reducing risk factor for sudden unexpected death.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"17 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91436192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontal lobe epilepsy (FLE) is a seizure disorder that commonly associated with functional motor deficits. While the source of these deficits is unknown, it is postulated that repeated seizure activity within the frontal lobe may impact the proximal motor network. To examine this hypothesis, motor networks were compared between participants with right FLE, left FLE, and controls using two methods. The first was a task-based fMRI study of brain activation during simple and complex motor tasks, and the second was a resting-state fMRI study of motor network connectivity. Both studies revealed motor network disturbances in participants with FLE, disturbances that were more pronounced in participants with higher seizure burden factors. These results demonstrate that motor networks are altered in patients with FLE, providing a possible underlying cause behind functional motor deficits in these patients.
{"title":"Examining motor network disturbances in patients with frontal lobe epilepsy using fMRI","authors":"K. Woodward, P. Federico","doi":"10.14800/MCE.247","DOIUrl":"https://doi.org/10.14800/MCE.247","url":null,"abstract":"Frontal lobe epilepsy (FLE) is a seizure disorder that commonly associated with functional motor deficits. While the source of these deficits is unknown, it is postulated that repeated seizure activity within the frontal lobe may impact the proximal motor network. To examine this hypothesis, motor networks were compared between participants with right FLE, left FLE, and controls using two methods. The first was a task-based fMRI study of brain activation during simple and complex motor tasks, and the second was a resting-state fMRI study of motor network connectivity. Both studies revealed motor network disturbances in participants with FLE, disturbances that were more pronounced in participants with higher seizure burden factors. These results demonstrate that motor networks are altered in patients with FLE, providing a possible underlying cause behind functional motor deficits in these patients.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81495934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epilepsy of infancy with migrating focal seizures (EIMFS) and a severe form of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) are strikingly different epilepsy syndromes, which have very recently been associated with mutations in the same gene. EIMFS is a rare early infantile epileptic encephalopathy characterised by heterogeneous migrating focal seizures, and associated with arrest or regression of development resulting in profound disability. In contrast, ADNFLE begins in mid-childhood and is characterized by clusters of motor seizures arising from sleep and is associated with major comorbidities of intellectual disability and psychiatric features. Whole exome sequencing of patients with EIMFS and severe ADNFLE has revealed a number of KCNT1 mutations with 100% penetrance, many of which are de novo . KCNT1 , widely expressed in the mammalian central nervous system, encodes a potassium channel that is activated by large elevations in intracellular sodium, which occur during normal physiological signalling in the nervous system. While KCNT1 channels are thought to play important roles in regulating neuronal excitability, their precise contribution to electrical activity differs in different neuronal cell types. KCNT1 disorders are resistant to standard anti-epileptic drugs and have a severe prognosis, creating an urgent need for novel therapies. Several studies have demonstrated that antiarrhythmic compounds, such as quinidine, bepridil and clofilium are effective blockers of KCNT1 channels and despite their known adverse effect profile our recent study suggests that they may hold promise as effective therapies in EIMFS. This research highlight describes this study, evaluating the electrophysiological and pharmacological gain-of-function phenotype of KCNT1 mutations in vitro and examining the neurodevelopmental time frame for the potential contribution of this channel to neuronal excitability in vivo .
{"title":"KCNT1 gain-of-function mutations linked to human epilepsy are modulated by quinidine","authors":"C. Milligan, Melody Li, S. Petrou","doi":"10.14800/MCE.220","DOIUrl":"https://doi.org/10.14800/MCE.220","url":null,"abstract":"Epilepsy of infancy with migrating focal seizures (EIMFS) and a severe form of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) are strikingly different epilepsy syndromes, which have very recently been associated with mutations in the same gene. EIMFS is a rare early infantile epileptic encephalopathy characterised by heterogeneous migrating focal seizures, and associated with arrest or regression of development resulting in profound disability. In contrast, ADNFLE begins in mid-childhood and is characterized by clusters of motor seizures arising from sleep and is associated with major comorbidities of intellectual disability and psychiatric features. Whole exome sequencing of patients with EIMFS and severe ADNFLE has revealed a number of KCNT1 mutations with 100% penetrance, many of which are de novo . KCNT1 , widely expressed in the mammalian central nervous system, encodes a potassium channel that is activated by large elevations in intracellular sodium, which occur during normal physiological signalling in the nervous system. While KCNT1 channels are thought to play important roles in regulating neuronal excitability, their precise contribution to electrical activity differs in different neuronal cell types. KCNT1 disorders are resistant to standard anti-epileptic drugs and have a severe prognosis, creating an urgent need for novel therapies. Several studies have demonstrated that antiarrhythmic compounds, such as quinidine, bepridil and clofilium are effective blockers of KCNT1 channels and despite their known adverse effect profile our recent study suggests that they may hold promise as effective therapies in EIMFS. This research highlight describes this study, evaluating the electrophysiological and pharmacological gain-of-function phenotype of KCNT1 mutations in vitro and examining the neurodevelopmental time frame for the potential contribution of this channel to neuronal excitability in vivo .","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81602393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4 th -7 th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9 th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9 th , suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.
{"title":"Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE). Is it related with SUDEP?","authors":"A. Lazarowski","doi":"10.14800/MCE.66","DOIUrl":"https://doi.org/10.14800/MCE.66","url":null,"abstract":"Patients with refractory epilepsy (RE) have increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), where acute and fatal heart failure is suspected. High seizure frequency, polypharmacy, changes in dosing, persistent low AED levels or poor adherence to therapy are the greatest risk factors of SUDEP and are also features observed in RE. We evaluated the progressive P-gp overexpression in heart, related with the development of fatal status epilepticus (FSE) after experimental repetitive seizures (ERS). Male Wistar rats (180–230g) were daily injected (i.p) with Pentylenetetrazole (PTZ; 45mg/kg; n=18) or saline (Controls; n=6). Severity of seizures was recorded. Four PTZ-treated rats were sacrificed at 4 th -7 th day respectively. Ten remaining rats, underwent same treatment until develop fatal status epilepticus (FSE). Brains and hearts were studied by immunofluorecent method for P-glycoptrotein (P-gp) expression. Seizures were observed each day of PTZ treatment, associated with a progressive P-gp overexpression in heart and FSE at 9 th day. Using the same PTZ model, we previously demonstrated that progressive brain P-gp overexpression contributes to cell membrane depolarization of hippocampus and neocortex. These are the first evidences showing that ERS induces a simultaneous and progressive P-gp overexpression in brain and heart associated with FSE, and suggests a role for this pattern expression of P-gp as risk factor for death during SE. The simultaneous and spontaneous death of all animals during SE observed only at day 9 th , suggest that a higher P-gp overexpression in cardiomyocytes could play a role in SUDEP, however, because it is only a study descriptive, further researches are needed to confirm this hypothesis.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72848336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Postictal headache (PIH) is defined by the International Classification of Headache Disorders, third edition beta (ICHD-3 beta), as “headache caused by and occurring within 3 hours after an epileptic seizure, and remitting spontaneously within 72 hours after seizure termination”. People at highest risk of suffering PIH are who have generalized tonic-seizures (GTCSs) and a history of interictal headaches. An occipital epileptogenic focus may be an additional risk factor. Also PIH frequently have characteristics of migraine, the diagnostic criteria of “headache with features of tension-type headache or, in a patient with migraine, of migraine headache” in ICHD-2 has been ruled out from the ICDH-3. The high percentage of PIH in patients with epilepsy which really burden patient’s daily life. For purposes of comparison, trials should adhere to a unified definition of PIH, and ICHD-3 beta revised the ICHD-2 definition which widens the inclusion criteria to any headache attributed to a seizure and following it. In order to improve the diagnosis and management of this symptom, clinicians should pay more attention to epileptic patients with PIH.
{"title":"Postictal headache in epileptic patients","authors":"Xiang-Qing Wang, Shengyuan Yu","doi":"10.14800/MCE.197","DOIUrl":"https://doi.org/10.14800/MCE.197","url":null,"abstract":"Postictal headache (PIH) is defined by the International Classification of Headache Disorders, third edition beta (ICHD-3 beta), as “headache caused by and occurring within 3 hours after an epileptic seizure, and remitting spontaneously within 72 hours after seizure termination”. People at highest risk of suffering PIH are who have generalized tonic-seizures (GTCSs) and a history of interictal headaches. An occipital epileptogenic focus may be an additional risk factor. Also PIH frequently have characteristics of migraine, the diagnostic criteria of “headache with features of tension-type headache or, in a patient with migraine, of migraine headache” in ICHD-2 has been ruled out from the ICDH-3. The high percentage of PIH in patients with epilepsy which really burden patient’s daily life. For purposes of comparison, trials should adhere to a unified definition of PIH, and ICHD-3 beta revised the ICHD-2 definition which widens the inclusion criteria to any headache attributed to a seizure and following it. In order to improve the diagnosis and management of this symptom, clinicians should pay more attention to epileptic patients with PIH.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82724338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite several studies there are still some issues concerning the correct diagnosis of epilepsy that should be distinguished from many other critical symptoms and diseases. Moreover, the assessment of a specific epileptic syndrome can have some degree of uncertainty. In this research highlight we discussed the findings of our recent study that demonstrated that at the onset of seizures an initial diagnosis is possible in the majority of cases; epilepsy syndromes can be identified at the time of the initial diagnosis and, at follow up, this diagnosis has not to be revised in 90% of the cases. Moreover, we analysed the main data form literature concerning the difficulties of the epilepsy syndromes diagnosis
{"title":"DIAGNOSIS OF EPILEPSY AFTER A FIRST UNPROVOKED SEIZURE: THE DIFFERENT ASPECTS OF A SINGLE PROBLEM","authors":"A. Verrotti, R. d’Alonzo, D. Laino","doi":"10.14800/MCE.165","DOIUrl":"https://doi.org/10.14800/MCE.165","url":null,"abstract":"Despite several studies there are still some issues concerning the correct diagnosis of epilepsy that should be distinguished from many other critical symptoms and diseases. Moreover, the assessment of a specific epileptic syndrome can have some degree of uncertainty. In this research highlight we discussed the findings of our recent study that demonstrated that at the onset of seizures an initial diagnosis is possible in the majority of cases; epilepsy syndromes can be identified at the time of the initial diagnosis and, at follow up, this diagnosis has not to be revised in 90% of the cases. Moreover, we analysed the main data form literature concerning the difficulties of the epilepsy syndromes diagnosis","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89136156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current anti-epileptic drugs (AEDs) primarily act by decreasing excitation or increasing inhibition of the neuronal network. This is achieved by inactivating Na + or Ca 2+ ion channels and decreasing glutamate release or by enhancing GABAergic influence. Despite using these AEDs, approximately 30% of epileptic patients remain intractable. As a consequence, there is a clear need to develop new AEDs that may work via novel mechanisms to provide greater efficacy. With this in mind, we investigated whether isovaline, a unique amino acid with a similar chemical structure to glycine and GABA, could fill this role. Previously, we showed that isovaline attenuated seizure-like events (SLEs) in vitro via a novel mechanism. In this research highlight, we discuss our latest published findings which demonstrate the efficacy of isovaline in an in vivo rat model of epilepsy.
{"title":"Isovaline: A unique amino acid with antiepileptic drug properties","authors":"W. Yu, Damian S Shin","doi":"10.14800/MCE.179","DOIUrl":"https://doi.org/10.14800/MCE.179","url":null,"abstract":"Current anti-epileptic drugs (AEDs) primarily act by decreasing excitation or increasing inhibition of the neuronal network. This is achieved by inactivating Na + or Ca 2+ ion channels and decreasing glutamate release or by enhancing GABAergic influence. Despite using these AEDs, approximately 30% of epileptic patients remain intractable. As a consequence, there is a clear need to develop new AEDs that may work via novel mechanisms to provide greater efficacy. With this in mind, we investigated whether isovaline, a unique amino acid with a similar chemical structure to glycine and GABA, could fill this role. Previously, we showed that isovaline attenuated seizure-like events (SLEs) in vitro via a novel mechanism. In this research highlight, we discuss our latest published findings which demonstrate the efficacy of isovaline in an in vivo rat model of epilepsy.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74680079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Close relationships between attention deficit hyperactivity disorder (ADHD) and epilepsy has been suggested due to prevalence of ADHD symptoms among patients with epilepsy than in the general population. Like epilepsy-depression connection, bi-directional relationships are suggested to underlie the predisposition of patients with ADHD to epilepsy and vice versa. Spontaneously hypertensive rats (SHRs) are characterized with typical behavioral symptoms such as hyperactivity, an attention deficit and impulsiveness, deficient sustained attention and decreased monoamine functioning. Our experimental findings suggest that SHRs might be used as a relevant model of comorbidity between ADHD and epilepsy. Spontaneously hypertensive rats demonstrate abnormal electrophysiological and behavioral characteristics as well as monoamine deficit in the frontal cortex and the hippocampus, which are also evident in epileptic rats. In addition, SHRs shows higher seizure susceptibility in models of temporal lobe epilepsy and disturbed circadian rhythms. Taken together, experimental findings suggest that SHRs could be used to explore the mechanism underlying bi-directional link of ADHD and epilepsy and as a screening method for mechanism-driven therapeutic approaches.
{"title":"Finding a model for comorbidity between attention deficit hyperactivity disorder and epilepsy","authors":"J. Tchekalarova","doi":"10.14800/MCE.147","DOIUrl":"https://doi.org/10.14800/MCE.147","url":null,"abstract":"Close relationships between attention deficit hyperactivity disorder (ADHD) and epilepsy has been suggested due to prevalence of ADHD symptoms among patients with epilepsy than in the general population. Like epilepsy-depression connection, bi-directional relationships are suggested to underlie the predisposition of patients with ADHD to epilepsy and vice versa. Spontaneously hypertensive rats (SHRs) are characterized with typical behavioral symptoms such as hyperactivity, an attention deficit and impulsiveness, deficient sustained attention and decreased monoamine functioning. Our experimental findings suggest that SHRs might be used as a relevant model of comorbidity between ADHD and epilepsy. Spontaneously hypertensive rats demonstrate abnormal electrophysiological and behavioral characteristics as well as monoamine deficit in the frontal cortex and the hippocampus, which are also evident in epileptic rats. In addition, SHRs shows higher seizure susceptibility in models of temporal lobe epilepsy and disturbed circadian rhythms. Taken together, experimental findings suggest that SHRs could be used to explore the mechanism underlying bi-directional link of ADHD and epilepsy and as a screening method for mechanism-driven therapeutic approaches.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87039964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sudden unexpected death in epilepsy (SUDEP) accounts for 5-30% of deaths in patients with epilepsy. Past research has attempted to reveal these mechanisms, but the specific risk factors and pathophysiology have not been established. Inherited lethal cardiac arrhythmias can be erroneously diagnosed as epilepsy. A diagnosis of coexistent epilepsy cannot be completely excluded in the inherited cardiac arrhythmias but the differential diagnosis is often challenged. SUDEP may be attributed to seizure-induced fatal cardiac arrhythmias or cardiopulmonary dysfunction as a secondary cause. The expanding knowledge base has increased the understanding of the structure-function and genotype-phenotype relationships of ion channels and has provided insights into the pathophysiological basis of common diseases such as cardiac arrhythmias and epilepsy. In this review, the mechanisms for SUDEP and the possible relationships between epilepsy and inherited cardiac arrhythmias as “neuro-cardiac channelopathy” have been discussed based on clinical and genetic evidence.
{"title":"Coexistence of Inherited Cardiac Arrhythmia in Epilepsy as Neuro-cardiac Channelopathy: From Hypothesis to Evidence","authors":"C. Omichi","doi":"10.14800/MCE.153","DOIUrl":"https://doi.org/10.14800/MCE.153","url":null,"abstract":"Sudden unexpected death in epilepsy (SUDEP) accounts for 5-30% of deaths in patients with epilepsy. Past research has attempted to reveal these mechanisms, but the specific risk factors and pathophysiology have not been established. Inherited lethal cardiac arrhythmias can be erroneously diagnosed as epilepsy. A diagnosis of coexistent epilepsy cannot be completely excluded in the inherited cardiac arrhythmias but the differential diagnosis is often challenged. SUDEP may be attributed to seizure-induced fatal cardiac arrhythmias or cardiopulmonary dysfunction as a secondary cause. The expanding knowledge base has increased the understanding of the structure-function and genotype-phenotype relationships of ion channels and has provided insights into the pathophysiological basis of common diseases such as cardiac arrhythmias and epilepsy. In this review, the mechanisms for SUDEP and the possible relationships between epilepsy and inherited cardiac arrhythmias as “neuro-cardiac channelopathy” have been discussed based on clinical and genetic evidence.","PeriodicalId":18603,"journal":{"name":"Molecular & Cellular Epilepsy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84145799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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