Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epile... more Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/...
Summary In order to validate the ability of ictal single photon emission computed tomography (SPE... more Summary In order to validate the ability of ictal single photon emission computed tomography (SPECT) to localize the epileptogenic zone (EZ) in children, we compared in 20 patients aged from 10 months to 17 years (mean 6.5 years) the topography of the area of increased ictal perfusion (IPA), determined on the basis of ictal minus interictal scan values, with that
Past studies have been unable to confirm whether early seizures predispose to epilepsy in adults.... more Past studies have been unable to confirm whether early seizures predispose to epilepsy in adults. Seizures in infancy were classically thought to cause brain lesions that led to epilepsy in adulthood. However, these infants were not thought to have epilepsy, but acute events that included seizures. Accumulating evidence suggests that early seizures may be associated with, or cause, brain damage; or alternatively, they may be the first expression of a genetic or lesional predisposition to epilepsy. The course of early seizures ranges from transient to life-long, depending on epilepsy syndrome, causes, and treatment. The main factors that determine late or persisting epilepsy after the occurrence of early seizures are protracted seizures, tonic seizures, and involvement of mesial temporal structures. A developmental approach to seizure disorders will aid understanding of epilepsy in adults and improve the design of antiepileptic agents for children and adults.
Summary Febrile seizures (FS) syndromes exhibit major clinical and genetic heterogeneity. We repo... more Summary Febrile seizures (FS) syndromes exhibit major clinical and genetic heterogeneity. We report a clinical and genetic study of three families with simple FS segregat- ing as an autosomal dominant (AD) trait with high penetrance. All affected members presented a homo- geneous phenotype of simple FS. The FS ceased before the age of 5 years. Among the 29 affected family
This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcar... more This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcarbazepine as combination therapy in 112 children 2 to 12 years old with inadequately controlled epilepsy. Part I was a pharmacokinetic study in children stratified by age (2-5 years and 6-12 years) and randomized to receive a single oxcarbazepine dose of 5 mg/kg or 15 mg/kg. Mean specific AUC
Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset charact... more Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset characterized by multiple generalized types of seizures including myoclonic astatic seizures, generalized spike waves and cognitive deterioration. This condition has been reported in a few patients in generalized epilepsy with febrile seizures plus (GEFS+) families and MAE has been considered, like severe myoclonic epilepsy of infancy (SMEI), to
To explore whether attention, memory, and behavior would be more affected in children with fronta... more To explore whether attention, memory, and behavior would be more affected in children with frontal lobe epilepsy than in children with other types of epilepsy, we compared 16 children with frontal lobe epilepsy (FLE), 8 with temporal lobe epilepsy (TLE), and 8 with generalized absence (GEA) seizures on the Performance Speed (PS) and Freedom of Distraction (FD) indices of the
Purpose: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epil... more Purpose: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). Methods: We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms
The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes cur... more The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.
Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new... more Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. Methods: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and
Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel o... more Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel of refractory epilepsy syndromes has not been entirely evaluated prospectively. In order to study the efficacy and safety of LVT as adjunctive therapy according to syndromes, we included 102 patients with refractory seizures (6 months to 15 years) in a prospective open-labeled trial. The responder rate was respectively 36% and 32% at 3 and 6 months with 6% and 7% patients becoming seizure free. Among the responders at 6 months (n=33), seizure frequency decreased by 66% and 79% at 3 and 6 months LVT compared to baseline. The highest benefit was for CSWS patients with 2/3 responders, 50% seizure free and no aggravation. LVT provided respectively 39% and 42% responders in focal and absence epilepsies. Infantile spasms and Dravet syndrome experienced the lowest efficacy. No patient with myoclonic-astatic epilepsy or Lennox-Gastaut syndrome was aggravated. LVT dose over 40 mg/kg/d was associated with a lower response rate. Tolerability was excellent. In spite of a small sample, we assume that CSWS is a good candidate for a randomized-controlled trial with LVT.
Disease-causing mutations in ion channels generally alter intrinsic gating properties such as act... more Disease-causing mutations in ion channels generally alter intrinsic gating properties such as activation, inactivation, and voltage dependence. We examined nine different mutations of the KCNT1 (Slack) Na(+)-activated K(+) channel that give rise to three distinct forms of epilepsy. All produced many-fold increases in current amplitude compared to the wild-type channel. This could not be accounted for by increases in the intrinsic open probability of individual channels. Rather, greatly increased opening was a consequence of cooperative interactions between multiple channels in a patch. The degree of cooperative gating was much greater for all of the mutant channels than for the wild-type channel, and could explain increases in current even in a mutant with reduced unitary conductance. We also found that the same mutation gave rise to different forms of epilepsy in different individuals. Our findings indicate that a major consequence of these mutations is to alter channel-channel int...
Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a ... more Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. Methods: Voxel-based analyses of cerebral glucose metabolism
... LOADING... WHAT IS WEST SYNDROME? Olivier Dulac, Christine Soufflet, Catherine Chiron, and An... more ... LOADING... WHAT IS WEST SYNDROME? Olivier Dulac, Christine Soufflet, Catherine Chiron, and Anna Kaminska I. I ntroduction II. Site of Onset of Spasms VIII. ... 134, 696-700. Tsao, CY,Luquette, M., Rusin,JA, Herr, GM, Kien, CL, and Morrow, G., III (1997). ...
Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epile... more Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/...
Summary In order to validate the ability of ictal single photon emission computed tomography (SPE... more Summary In order to validate the ability of ictal single photon emission computed tomography (SPECT) to localize the epileptogenic zone (EZ) in children, we compared in 20 patients aged from 10 months to 17 years (mean 6.5 years) the topography of the area of increased ictal perfusion (IPA), determined on the basis of ictal minus interictal scan values, with that
Past studies have been unable to confirm whether early seizures predispose to epilepsy in adults.... more Past studies have been unable to confirm whether early seizures predispose to epilepsy in adults. Seizures in infancy were classically thought to cause brain lesions that led to epilepsy in adulthood. However, these infants were not thought to have epilepsy, but acute events that included seizures. Accumulating evidence suggests that early seizures may be associated with, or cause, brain damage; or alternatively, they may be the first expression of a genetic or lesional predisposition to epilepsy. The course of early seizures ranges from transient to life-long, depending on epilepsy syndrome, causes, and treatment. The main factors that determine late or persisting epilepsy after the occurrence of early seizures are protracted seizures, tonic seizures, and involvement of mesial temporal structures. A developmental approach to seizure disorders will aid understanding of epilepsy in adults and improve the design of antiepileptic agents for children and adults.
Summary Febrile seizures (FS) syndromes exhibit major clinical and genetic heterogeneity. We repo... more Summary Febrile seizures (FS) syndromes exhibit major clinical and genetic heterogeneity. We report a clinical and genetic study of three families with simple FS segregat- ing as an autosomal dominant (AD) trait with high penetrance. All affected members presented a homo- geneous phenotype of simple FS. The FS ceased before the age of 5 years. Among the 29 affected family
This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcar... more This two-part, open-label study evaluated the pharmacokinetics, safety, and tolerability of oxcarbazepine as combination therapy in 112 children 2 to 12 years old with inadequately controlled epilepsy. Part I was a pharmacokinetic study in children stratified by age (2-5 years and 6-12 years) and randomized to receive a single oxcarbazepine dose of 5 mg/kg or 15 mg/kg. Mean specific AUC
Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset charact... more Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset characterized by multiple generalized types of seizures including myoclonic astatic seizures, generalized spike waves and cognitive deterioration. This condition has been reported in a few patients in generalized epilepsy with febrile seizures plus (GEFS+) families and MAE has been considered, like severe myoclonic epilepsy of infancy (SMEI), to
To explore whether attention, memory, and behavior would be more affected in children with fronta... more To explore whether attention, memory, and behavior would be more affected in children with frontal lobe epilepsy than in children with other types of epilepsy, we compared 16 children with frontal lobe epilepsy (FLE), 8 with temporal lobe epilepsy (TLE), and 8 with generalized absence (GEA) seizures on the Performance Speed (PS) and Freedom of Distraction (FD) indices of the
Purpose: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epil... more Purpose: To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). Methods: We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms
The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes cur... more The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.
Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new... more Objective: To study the relationship between the plasma concentration of stiripentol (STP), a new antiepileptic drug, and its inhibitory effect on the formation of carbamazepine epoxide (CBZE) in epileptic children treated with carbamazepine (CBZ) either alone or in combination with another antiepileptic drug. Methods: Minimum plasma concentration of antiepileptic drugs was measured before initiation of STP therapy (day 0) and
Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel o... more Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel of refractory epilepsy syndromes has not been entirely evaluated prospectively. In order to study the efficacy and safety of LVT as adjunctive therapy according to syndromes, we included 102 patients with refractory seizures (6 months to 15 years) in a prospective open-labeled trial. The responder rate was respectively 36% and 32% at 3 and 6 months with 6% and 7% patients becoming seizure free. Among the responders at 6 months (n=33), seizure frequency decreased by 66% and 79% at 3 and 6 months LVT compared to baseline. The highest benefit was for CSWS patients with 2/3 responders, 50% seizure free and no aggravation. LVT provided respectively 39% and 42% responders in focal and absence epilepsies. Infantile spasms and Dravet syndrome experienced the lowest efficacy. No patient with myoclonic-astatic epilepsy or Lennox-Gastaut syndrome was aggravated. LVT dose over 40 mg/kg/d was associated with a lower response rate. Tolerability was excellent. In spite of a small sample, we assume that CSWS is a good candidate for a randomized-controlled trial with LVT.
Disease-causing mutations in ion channels generally alter intrinsic gating properties such as act... more Disease-causing mutations in ion channels generally alter intrinsic gating properties such as activation, inactivation, and voltage dependence. We examined nine different mutations of the KCNT1 (Slack) Na(+)-activated K(+) channel that give rise to three distinct forms of epilepsy. All produced many-fold increases in current amplitude compared to the wild-type channel. This could not be accounted for by increases in the intrinsic open probability of individual channels. Rather, greatly increased opening was a consequence of cooperative interactions between multiple channels in a patch. The degree of cooperative gating was much greater for all of the mutant channels than for the wild-type channel, and could explain increases in current even in a mutant with reduced unitary conductance. We also found that the same mutation gave rise to different forms of epilepsy in different individuals. Our findings indicate that a major consequence of these mutations is to alter channel-channel int...
Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a ... more Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. Methods: Voxel-based analyses of cerebral glucose metabolism
... LOADING... WHAT IS WEST SYNDROME? Olivier Dulac, Christine Soufflet, Catherine Chiron, and An... more ... LOADING... WHAT IS WEST SYNDROME? Olivier Dulac, Christine Soufflet, Catherine Chiron, and Anna Kaminska I. I ntroduction II. Site of Onset of Spasms VIII. ... 134, 696-700. Tsao, CY,Luquette, M., Rusin,JA, Herr, GM, Kien, CL, and Morrow, G., III (1997). ...
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