The Experts below are selected from a list of 483 Experts worldwide ranked by ideXlab platform
Ulrich Stephani - One of the best experts on this subject based on the ideXlab platform.
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SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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EMBC - SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and, 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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eeg fmri in Myoclonic Astatic Epilepsy doose syndrome
Neurology, 2014Co-Authors: Friederike Moeller, Ulrich Stephani, Kristina Groening, Jan Moehring, Hiltrud Muhle, Stephan Wolff, O Jansen, Michael SiniatchkinAbstract:Objective: To identify neuronal networks underlying generalized spike and wave discharges (GSW) in Myoclonic Astatic Epilepsy (MAE). Methods: Simultaneous EEG-fMRI recordings were performed in 13 children with MAE. Individual GSW-associated blood oxygenation level–dependent (BOLD) signal changes were analyzed in every patient. A group analysis was performed to determine common syndrome-specific hemodynamic changes across all patients. Results: GSW were recorded in 11 patients, all showing GSW-associated BOLD signal changes. Activation was detected in the thalamus (all patients), premotor cortex (6 patients), and putamen (6 patients). Deactivation was found in the default mode areas (7 patients). The group analysis confirmed activations in the thalamus, premotor cortex, putamen, and cerebellum and deactivations in the default mode network. Conclusions: In addition to the thalamocortical network, which is commonly found in idiopathic generalized epilepsies, GSW in patients with MAE are characterized by BOLD signal changes in brain structures associated with motor function. The results are in line with animal studies demonstrating that somatosensory cortex, putamen, and cerebellum are involved in the generation of Myoclonic seizures. The involvement of these structures might predispose to the typical seizure semiology of Myoclonic jerks observed in MAE.
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Myoclonic Astatic Epilepsy doose syndrome a lamotrigine responsive Epilepsy
European Journal of Paediatric Neurology, 2013Co-Authors: C Doege, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Rainer BoorAbstract:Abstract Purpose Myoclonic Astatic Epilepsy (MAE, Doose syndrome) is a difficult to treat idiopathic generalized Epilepsy of early childhood. MAE frequently shows the course of an epileptic encephalopathy and may result in permanent cognitive impairment. Systematic analyses on clinical effects of different AED combinations are still needed. The purpose of our study was to analyze the therapeutic effect of adjunctive lamotrigine (LTG) in pharmacoresistant MAE patients. Patients and methods In an exploratory, retrospective study, 10 pharmacoresistant MAE patients were included who had been admitted to the Northern German Epilepsy Center between 07/2007 and 12/2010 and had been treated with LTG. Documentation was performed with the electronic seizure diary Epivista ® . A total observation period of 32 weeks was defined: 8-week ‘pre LTG treatment phase’ (before starting with LTG), 16-week ‘titration phase’ (starting with very low LTG doses), 8-week ‘follow-up phase’. Seizure frequency, medication and adverse events were extracted from the electronic diary and evaluated in each particular patient. The individual reduction of seizure frequency per day was defined as primary outcome variable. Additionally, a dose-effect-relationship was analyzed for each patient. Results Six out of ten patients were seizure free during the follow-up phase. Statistical analysis indicated a significant seizure reduction in seven patients at follow-up compared to the pre LTG treatment phase. Seizure frequency did not significantly decrease in two patients and increased in one patient. A significant relationship between seizure frequency per day and LTG dosage during titration and follow-up phase could be demonstrated in nine patients. Group statistics using the exact Wilcoxon test revealed a significant reduction in seizure frequency ( p = 0.049, two-sided). Conclusion Our data provide evidence that adjunctive LTG is an eligible therapeutic option for the treatment of pharmacoresistant MAE and encourage further prospective studies to verify this observation.
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the natural history of Myoclonic Astatic Epilepsy doose syndrome and lennox gastaut syndrome
Epilepsia, 2006Co-Authors: Ulrich StephaniAbstract:Summary: The purpose of this article is to present a short review of the natural history of Myoclonic Astatic Epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). In the 1989 classification of the International League Against Epilepsy (ILAE, 1989), MAE and LGS were initially included in group 2.2: “Cryptogenic or symptomatic generalized epilepsies and syndromes.” The subsequent classification of the Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy (see Ref. 8) placed MAE in axis 3 in the “generalized Epilepsy” group and LGS, severe Myoclonic Epilepsy of infancy (SMEI or Dravet syndrome) and atypical benign partial Epilepsy/pseudo-Lennox syndrome (ABPE/PLS) in the “epileptic encephalopathy” group. The semiology of MAE and LGS and their differential diagnosis from SMEI and ABPE/PLS are described. Before the onset of SMEI, MAE, and ABPE/PLS, the development of the child is usually normal. In contrast, in LGS, development is frequently retarded at the onset, depending on the etiopathogenesis of the underlying brain disease. The course of MAE is highly variable with regard to seizure outcome (complete remission in some cases, persistent Epilepsy in others) and cognitive development (normal or delayed). The course of LGS and SMEI is generally poor, both with regard to the Epilepsy and to the cognitive development whereas the course and seizure outcome of ABPE/PLS is favorable; the patients will be seizure-free at puberty. However, the neuropsychological outcome is less favorable; most patients remain mentally retarded.
Michael Siniatchkin - One of the best experts on this subject based on the ideXlab platform.
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SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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EMBC - SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and, 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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Analysis of the effects of medication for the treatment of Epilepsy by ensemble Iterative Extended Kalman filtering
2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2018Co-Authors: Sidratul Moontaha, Andreas Galka, Thomas Meurer, Michael SiniatchkinAbstract:This paper proposes an objective methodology for the analysis of epileptic seizure count time series by developing a non-linear state space model. An iterative extended Kalman filter (IEKF) is employed for the estimation of the states of the non-linear state space model. In order to improve convergence of the IEKF, the recently proposed Levenberg-Marquardt variant of the IEKF is explored. As external inputs time-dependent dosages of several simultaneously administered anticonvulsants are included. The aim of the analysis is to decide whether each anticonvulsant decreases or increases the number of seizures per day. The performance of the analysis is analyzed for simulated data, as well as for real data from a patient suffering from Myoclonic-Astatic Epilepsy.
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EMBC - Analysis of the effects of medication for the treatment of Epilepsy by ensemble Iterative Extended Kalman filtering
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and, 2018Co-Authors: Sidratul Moontaha, Andreas Galka, Thomas Meurer, Michael SiniatchkinAbstract:This paper proposes an objective methodology for the analysis of epileptic seizure count time series by developing a non-linear state space model. An iterative extended Kalman filter (IEKF) is employed for the estimation of the states of the non-linear state space model. In order to improve convergence of the IEKF, the recently proposed Levenberg-Marquardt variant of the IEKF is explored. As external inputs time-dependent dosages of several simultaneously administered anticonvulsants are included. The aim of the analysis is to decide whether each anticonvulsant decreases or increases the number of seizures per day. The performance of the analysis is analyzed for simulated data, as well as for real data from a patient suffering from Myoclonic-Astatic Epilepsy.
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eeg fmri in Myoclonic Astatic Epilepsy doose syndrome
Neurology, 2014Co-Authors: Friederike Moeller, Ulrich Stephani, Kristina Groening, Jan Moehring, Hiltrud Muhle, Stephan Wolff, O Jansen, Michael SiniatchkinAbstract:Objective: To identify neuronal networks underlying generalized spike and wave discharges (GSW) in Myoclonic Astatic Epilepsy (MAE). Methods: Simultaneous EEG-fMRI recordings were performed in 13 children with MAE. Individual GSW-associated blood oxygenation level–dependent (BOLD) signal changes were analyzed in every patient. A group analysis was performed to determine common syndrome-specific hemodynamic changes across all patients. Results: GSW were recorded in 11 patients, all showing GSW-associated BOLD signal changes. Activation was detected in the thalamus (all patients), premotor cortex (6 patients), and putamen (6 patients). Deactivation was found in the default mode areas (7 patients). The group analysis confirmed activations in the thalamus, premotor cortex, putamen, and cerebellum and deactivations in the default mode network. Conclusions: In addition to the thalamocortical network, which is commonly found in idiopathic generalized epilepsies, GSW in patients with MAE are characterized by BOLD signal changes in brain structures associated with motor function. The results are in line with animal studies demonstrating that somatosensory cortex, putamen, and cerebellum are involved in the generation of Myoclonic seizures. The involvement of these structures might predispose to the typical seizure semiology of Myoclonic jerks observed in MAE.
Samuel F Berkovic - One of the best experts on this subject based on the ideXlab platform.
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glucose metabolism transporters and Epilepsy only glut1 has an established role
Epilepsia, 2014Co-Authors: Michael S Hildebrand, Saul A Mullen, John A Damiano, Ingrid E Scheffer, Susannah T Bellows, Karen L Oliver, Hanshenrik M Dahl, Samuel F BerkovicAbstract:Summary 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.
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glucose transporter 1 deficiency as a treatable cause of Myoclonic Astatic Epilepsy
JAMA Neurology, 2011Co-Authors: Saul A Mullen, Carla Marini, Arvid Suls, Elvio Della Giustina, Daniela Buti, Todor Arsov, John A Damiano, Kate M Lawrence, Peter De Jonghe, Samuel F BerkovicAbstract:Objective To determine if a significant proportion of patients with Myoclonic-Astatic Epilepsy (MAE) have glucose transporter 1 (GLUT1) deficiency. Design Genetic analysis. Setting Ambulatory and hospitalized care. Patients Eighty-four unrelated probands with MAE were phenotyped and SLC2A1 was sequenced and analyzed by multiplex ligation-dependent probe amplification. Any identified mutations were then screened in controls. Main Outcome Measure Any SLC2A1 mutations. Results Four of 84 probands with MAE had a mutation of SLC2A1 on sequencing. Multiplex ligation-dependent probe amplification analysis did not reveal any genomic rearrangements in 75 of the remaining cases; 5 could not be tested. Two patients with MAE with SLC2A1 mutations also developed paroxysmal exertional dyskinesia in childhood. Conclusions Five percent of our patients with MAE had SLC2A1 mutations, suggesting that patients with MAE should be tested for GLUT1 deficiency. Diagnosis of GLUT1 deficiency is a strong indication for early use of the ketogenic diet, which may substantially improve outcome of this severe disorder.
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absence epilepsies with widely variable onset are a key feature of familial glut1 deficiency
Neurology, 2010Co-Authors: Saul A Mullen, Arvid Suls, Samuel F Berkovic, P De Jonghe, Ingrid E SchefferAbstract:Background: Familial glucose transporter type 1 (GLUT1) deficiency due to autosomal dominant inheritance of SLC2A1 mutations is associated with paroxysmal exertional dyskinesia; Epilepsy and intellectual disability occur in some family members. We recently demonstrated that GLUT1 deficiency occurs in over 10% of patients with early-onset absence Epilepsy. Methods: This family study analyses the phenotypes in 2 kindreds segregating SLC2A1 mutations identified through probands with early-onset absence Epilepsy. One comprised 9 individuals with mutations over 3 generations; the other had 6 individuals over 2 generations. Results: Of 15 subjects with SLC2A1 mutations, Epilepsy occurred in 12. Absence seizures were the most prevalent seizure type (10/12), with onset from 3 to 34 years of age. Epilepsy phenotypes varied widely, including idiopathic generalized epilepsies (IGE) with absence (8/12), Myoclonic-Astatic Epilepsy (2/12), and focal Epilepsy (2/12). Paroxysmal exertional dyskinesia occurred in 7, and was subtle and universally undiagnosed prior to molecular diagnosis. There were 2 unaffected mutation carriers. Conclusions: GLUT1 deficiency is an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Individual cases may be phenotypically indistinguishable from common forms of IGE. Although subtle paroxysmal exertional dyskinesia is a helpful diagnostic clue, it is far from universal. The phenotypic spectrum of GLUT1 deficiency is considerably greater than previously recognized. Diagnosis of GLUT1 deficiency has important treatment and genetic counseling implications.
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clinical and molecular genetics of Myoclonic Astatic Epilepsy and severe Myoclonic Epilepsy in infancy dravet syndrome
Brain & Development, 2001Co-Authors: Robyn H Wallace, Ingrid E Scheffer, John C Mulley, Samuel F BerkovicAbstract:The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-Astatic Epilepsy (MAE) and severe Myoclonic Epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic Epilepsy syndrome generalized Epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.
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Clinical and molecular genetics of Myoclonic–Astatic Epilepsy and severe Myoclonic Epilepsy in infancy (Dravet syndrome)
Brain & Development, 2001Co-Authors: Ingrid E Scheffer, Robyn H Wallace, John C Mulley, Samuel F BerkovicAbstract:The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-Astatic Epilepsy (MAE) and severe Myoclonic Epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic Epilepsy syndrome generalized Epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.
Sarah Von Spiczak - One of the best experts on this subject based on the ideXlab platform.
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SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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EMBC - SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and, 2019Co-Authors: Sidratul Moontaha, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Andreas Galka, Sascha Scharlach, Thomas MeurerAbstract:In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.
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the role of slc2a1 mutations in Myoclonic Astatic Epilepsy and absence Epilepsy and the estimated frequency of glut1 deficiency syndrome
Epilepsia, 2015Co-Authors: Jan Petter Larsen, Shan Tang, Carla Marini, Sarah Von Spiczak, Katrine M Johannesen, Jakob Ek, Susanne Blichfeldt, Maria Kibaek, Sarah WeckhuysenAbstract:Summary The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood–brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of Epilepsy including early onset absence Epilepsy (EOAE), Myoclonic Astatic Epilepsy (MAE), and genetic generalized Epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of Epilepsy including MAE and absence Epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence Epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence Epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence Epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.
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Myoclonic Astatic Epilepsy doose syndrome a lamotrigine responsive Epilepsy
European Journal of Paediatric Neurology, 2013Co-Authors: C Doege, Ulrich Stephani, Michael Siniatchkin, Sarah Von Spiczak, Rainer BoorAbstract:Abstract Purpose Myoclonic Astatic Epilepsy (MAE, Doose syndrome) is a difficult to treat idiopathic generalized Epilepsy of early childhood. MAE frequently shows the course of an epileptic encephalopathy and may result in permanent cognitive impairment. Systematic analyses on clinical effects of different AED combinations are still needed. The purpose of our study was to analyze the therapeutic effect of adjunctive lamotrigine (LTG) in pharmacoresistant MAE patients. Patients and methods In an exploratory, retrospective study, 10 pharmacoresistant MAE patients were included who had been admitted to the Northern German Epilepsy Center between 07/2007 and 12/2010 and had been treated with LTG. Documentation was performed with the electronic seizure diary Epivista ® . A total observation period of 32 weeks was defined: 8-week ‘pre LTG treatment phase’ (before starting with LTG), 16-week ‘titration phase’ (starting with very low LTG doses), 8-week ‘follow-up phase’. Seizure frequency, medication and adverse events were extracted from the electronic diary and evaluated in each particular patient. The individual reduction of seizure frequency per day was defined as primary outcome variable. Additionally, a dose-effect-relationship was analyzed for each patient. Results Six out of ten patients were seizure free during the follow-up phase. Statistical analysis indicated a significant seizure reduction in seven patients at follow-up compared to the pre LTG treatment phase. Seizure frequency did not significantly decrease in two patients and increased in one patient. A significant relationship between seizure frequency per day and LTG dosage during titration and follow-up phase could be demonstrated in nine patients. Group statistics using the exact Wilcoxon test revealed a significant reduction in seizure frequency ( p = 0.049, two-sided). Conclusion Our data provide evidence that adjunctive LTG is an eligible therapeutic option for the treatment of pharmacoresistant MAE and encourage further prospective studies to verify this observation.
Shan Tang - One of the best experts on this subject based on the ideXlab platform.
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new smarca2 mutation in a patient with nicolaides baraitser syndrome and Myoclonic Astatic Epilepsy
American Journal of Medical Genetics Part A, 2017Co-Authors: Shan Tang, Elaine Hughes, Karine Lascelles, Michael A SimpsonAbstract:We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with Myoclonic Astatic Epilepsy, leading to reassessment and identification of Nicolaides–Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be associated with Nicolaides–Baraitser syndrome and adds to chromatin remodeling as a pathway for epileptogenesis. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.
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New SMARCA2 Mutation in a Patient with Nicolaides–Baraitser Syndrome and Myoclonic Astatic Epilepsy
American Journal of Medical Genetics Part A, 2016Co-Authors: Shan Tang, Elaine Hughes, Karine Lascelles, Michael A SimpsonAbstract:We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with Myoclonic Astatic Epilepsy, leading to reassessment and identification of Nicolaides–Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be associated with Nicolaides–Baraitser syndrome and adds to chromatin remodeling as a pathway for epileptogenesis. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.
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the role of slc2a1 mutations in Myoclonic Astatic Epilepsy and absence Epilepsy and the estimated frequency of glut1 deficiency syndrome
Epilepsia, 2015Co-Authors: Jan Petter Larsen, Shan Tang, Carla Marini, Sarah Von Spiczak, Katrine M Johannesen, Jakob Ek, Susanne Blichfeldt, Maria Kibaek, Sarah WeckhuysenAbstract:Summary The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood–brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of Epilepsy including early onset absence Epilepsy (EOAE), Myoclonic Astatic Epilepsy (MAE), and genetic generalized Epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of Epilepsy including MAE and absence Epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence Epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence Epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence Epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.
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dissecting the genetic basis of Myoclonic Astatic Epilepsy
Epilepsia, 2012Co-Authors: Shan TangAbstract:Summary Herman Doose first described the generalized childhood Epilepsy syndrome of Myoclonic Astatic Epilepsy (MAE) in 1970, attributing a genetic cause from this first description. However, although the International League Against Epilepsy (ILAE) defined criteria for MAE in 1989, the diagnostic boundaries of the syndrome continue to be debated. Moreover, 40 years since Doose's first description of MAE, although a genetic predisposition is acknowledged and many studies have demonstrated familial aggregation of seizures within MAE families, the actual genetic determinants of MAE still remain unknown. Although initially thought to be within the same spectrum as severe Myoclonic Epilepsy of infancy, the exclusion of SCN1A mutations in non-generalized Epilepsy with febrile seizures plus (GEFS+) MAE cases has confirmed the genetic distinction of MAE. In this critical review, we shall trace the historical evolution of concepts around MAE and its distinction from Lennox-Gastaut syndrome, review the described phenotypic features of MAE from updated studies that will allow its distinction from other overlap Epilepsy syndromes, review the evidence of genetic influences and clues for genetic heterogeneity, and discuss strategies that may be helpful in elucidating the etiology of MAE in light of current genetic techniques.
