A history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic ... more A history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic factors is unclear. This analysis evaluated the relationship between febrile seizures and epilepsy. Information on the history of seizures was obtained by a questionnaire from twin pairs in the Mid-Atlantic, Danish, and Norwegian Twin Registries. The information was verified using medical records and detailed clinical and family interviews. The initial study evaluated the genetic epidemiology of febrile seizures in this population. Further information was analyzed and used to evaluate genetic associations of different febrile seizure subtypes. Histories of febrile seizures were validated in 1051 twins in 900 pairs. The febrile seizure type was classified as simple, complex, or febrile status epilepticus. There were 61% simple, 12% complex, and 7% febrile status epilepticus. There were 78 twins who developed epilepsy. The highest rate of epilepsy (22.2%) occurred in the febrile status epilepticus group. Concordance was highest in simple group. A twin with febrile status epilepticus is at the highest risk of developing epilepsy, but simple febrile seizures gave the highest risk for the unaffected twin to develop seizures or other neurological issues. These results are consistent with previous findings. There is a subgroup of febrile seizures that can be associated with long-term consequences. The subgroup can be associated with a significant financial and emotional burden. It is currently not possible to accurately identify which children will develop recurrent febrile seizures, epilepsy, or neuropsychological comorbidities. Further studies are needed.
Several new agents have recently become available for the long-term treatment of epilepsy. Until ... more Several new agents have recently become available for the long-term treatment of epilepsy. Until now, there has been little change for the acute management of seizures. Three new agents may alter our present practice. Fosphenytoin has recently been approved as a substitute for parenteral phenytoin. It provides similar efficacy without the risk for infusion site injury while allowing greater flexibility in intravenous solutions. Intravenous valproate adds flexibility for patients on valproate, allowing patients to be rapidly loaded. In addition, it will prevent patients from having to change seizure medications when intervening medical illness or surgery do not allow medications by mouth. Viscous diazepam solution for rectal administration will allow for safe and effective treatment for seizures at home and will potentially decrease emergency department services and hospitalization.
Patients with epilepsy may sometimes require antiepileptic drugs (AEDs) parenterally. This study ... more Patients with epilepsy may sometimes require antiepileptic drugs (AEDs) parenterally. This study assessed the safety and tolerability of valproate sodium injection (IV valproate)(Depacon, Abbott Laboratories, Abbott Park, IL), given by intravenous infusion, ...
The purpose of these investigations was to determine from combined data the response to rectal di... more The purpose of these investigations was to determine from combined data the response to rectal diazepam (DZP) gel (Diastat [Athena Neurosciences, South San Francisco, CA]) in home treatment of children with episodes of acute repetitive seizures (ARS). A subset of patients aged 2-17 years were selected from two prospective placebo-controlled studies of children and adults. In both studies a prospective, double-blind, placebo-controlled design was used. The treatment groups (68 DZP; 65 placebo) did not differ significantly in age, race, seizure type or etiology, or in the median number of ARS episodes per month before study entry. DZP-treated children demonstrated a significant reduction in median seizure frequency compared with the placebo group (0.00 vs 0.25 seizures per hour, P = 0.001). Significantly more DZP-treated children remained seizure free during the observation period (40 vs 20, P = 0.001). Somnolence was the only adverse effect present significantly more often in the DZP-treated children (25.0% vs 7.7%, P = 0.0095). There were no instances of serious respiratory depression. Rectal DZP was demonstrated to be an effective and safe treatment to abort an episode of ARS in a child and, additionally, lessened the likelihood of seizure recurrence within the next 12 hours.
A child with neurofibromatosis had hypertension and acute hemiplegia resulting from both renal an... more A child with neurofibromatosis had hypertension and acute hemiplegia resulting from both renal and cerebral vascular occlusive disease. This case illustrates the importance of recognizing surgical antihypertensive therapy was attempted, and may have contributed to rapid neurologic deterioration. Children with neurofibromatosis and hypertension require a careful neurologic evaluation, including computed tomography, before therapy.
Pulmonary edema complicating generalized tonic-clonic seizures has rarely been reported in childr... more Pulmonary edema complicating generalized tonic-clonic seizures has rarely been reported in children, although it has been well documented in adults. We report two patients, aged 8 and 9 years, who developed clinical and radiographic evidence of the condition. Fever, leukocytosis, and arterial hypoxemia are seen in the absence of cardiac dysfunction or infection. Rapid and complete recovery is to be expected if supportive therapy is instituted. Since these patients had no underlying cardiac pathology, control of the seizures will prevent further episodes.
To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjun... more To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjunctive treatment of partial seizures. Patient compliance is a key feature of successful outpatient pharmacologic therapy for epilepsy, and one aspect of compliance is simplicity of initiation. By using a rapid titration rate, leading to a rapid therapeutic gabapentin dose, perhaps there could be an improvement with compliance. Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin (following a blinded placebo period of an undisclosed number of days) as either a Slow initiation (300 mg day 1, 600 mg day 2, then 900 mg/day) or a Rapid initiation (900 mg/day immediately following the placebo lead-in). Starting gabapentin therapy at an initial therapeutic dosage of 900 mg/day is well tolerated by patients with epilepsy and is as safe as initiating with a titration schedule over 3 days. Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group. Initiation of gabapentin at 900 mg/day is as well tolerated as is a 3-day titration, except for a higher incidence of dizziness.
Many IV antiepileptic drugs administered in emergency situations to patients with prolonged seizu... more Many IV antiepileptic drugs administered in emergency situations to patients with prolonged seizures have serious adverse effects. For this reason, the authors conducted a multicenter, open-label, prospective, dose-escalation study of IV valproate sodium administered to patients with epilepsy at rates of infusion of up to 6 mg/kg/minute and doses of up to 30 mg/kg. Valproate sodium had no clinically significant negative effects on blood pressure and pulse rate and caused only mild-to-moderate, reversible adverse events.
A history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic ... more A history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic factors is unclear. This analysis evaluated the relationship between febrile seizures and epilepsy. Information on the history of seizures was obtained by a questionnaire from twin pairs in the Mid-Atlantic, Danish, and Norwegian Twin Registries. The information was verified using medical records and detailed clinical and family interviews. The initial study evaluated the genetic epidemiology of febrile seizures in this population. Further information was analyzed and used to evaluate genetic associations of different febrile seizure subtypes. Histories of febrile seizures were validated in 1051 twins in 900 pairs. The febrile seizure type was classified as simple, complex, or febrile status epilepticus. There were 61% simple, 12% complex, and 7% febrile status epilepticus. There were 78 twins who developed epilepsy. The highest rate of epilepsy (22.2%) occurred in the febrile status epilepticus group. Concordance was highest in simple group. A twin with febrile status epilepticus is at the highest risk of developing epilepsy, but simple febrile seizures gave the highest risk for the unaffected twin to develop seizures or other neurological issues. These results are consistent with previous findings. There is a subgroup of febrile seizures that can be associated with long-term consequences. The subgroup can be associated with a significant financial and emotional burden. It is currently not possible to accurately identify which children will develop recurrent febrile seizures, epilepsy, or neuropsychological comorbidities. Further studies are needed.
Several new agents have recently become available for the long-term treatment of epilepsy. Until ... more Several new agents have recently become available for the long-term treatment of epilepsy. Until now, there has been little change for the acute management of seizures. Three new agents may alter our present practice. Fosphenytoin has recently been approved as a substitute for parenteral phenytoin. It provides similar efficacy without the risk for infusion site injury while allowing greater flexibility in intravenous solutions. Intravenous valproate adds flexibility for patients on valproate, allowing patients to be rapidly loaded. In addition, it will prevent patients from having to change seizure medications when intervening medical illness or surgery do not allow medications by mouth. Viscous diazepam solution for rectal administration will allow for safe and effective treatment for seizures at home and will potentially decrease emergency department services and hospitalization.
Patients with epilepsy may sometimes require antiepileptic drugs (AEDs) parenterally. This study ... more Patients with epilepsy may sometimes require antiepileptic drugs (AEDs) parenterally. This study assessed the safety and tolerability of valproate sodium injection (IV valproate)(Depacon, Abbott Laboratories, Abbott Park, IL), given by intravenous infusion, ...
The purpose of these investigations was to determine from combined data the response to rectal di... more The purpose of these investigations was to determine from combined data the response to rectal diazepam (DZP) gel (Diastat [Athena Neurosciences, South San Francisco, CA]) in home treatment of children with episodes of acute repetitive seizures (ARS). A subset of patients aged 2-17 years were selected from two prospective placebo-controlled studies of children and adults. In both studies a prospective, double-blind, placebo-controlled design was used. The treatment groups (68 DZP; 65 placebo) did not differ significantly in age, race, seizure type or etiology, or in the median number of ARS episodes per month before study entry. DZP-treated children demonstrated a significant reduction in median seizure frequency compared with the placebo group (0.00 vs 0.25 seizures per hour, P = 0.001). Significantly more DZP-treated children remained seizure free during the observation period (40 vs 20, P = 0.001). Somnolence was the only adverse effect present significantly more often in the DZP-treated children (25.0% vs 7.7%, P = 0.0095). There were no instances of serious respiratory depression. Rectal DZP was demonstrated to be an effective and safe treatment to abort an episode of ARS in a child and, additionally, lessened the likelihood of seizure recurrence within the next 12 hours.
A child with neurofibromatosis had hypertension and acute hemiplegia resulting from both renal an... more A child with neurofibromatosis had hypertension and acute hemiplegia resulting from both renal and cerebral vascular occlusive disease. This case illustrates the importance of recognizing surgical antihypertensive therapy was attempted, and may have contributed to rapid neurologic deterioration. Children with neurofibromatosis and hypertension require a careful neurologic evaluation, including computed tomography, before therapy.
Pulmonary edema complicating generalized tonic-clonic seizures has rarely been reported in childr... more Pulmonary edema complicating generalized tonic-clonic seizures has rarely been reported in children, although it has been well documented in adults. We report two patients, aged 8 and 9 years, who developed clinical and radiographic evidence of the condition. Fever, leukocytosis, and arterial hypoxemia are seen in the absence of cardiac dysfunction or infection. Rapid and complete recovery is to be expected if supportive therapy is instituted. Since these patients had no underlying cardiac pathology, control of the seizures will prevent further episodes.
To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjun... more To compare the tolerability of two different dose-initiation regimens of gabapentin for the adjunctive treatment of partial seizures. Patient compliance is a key feature of successful outpatient pharmacologic therapy for epilepsy, and one aspect of compliance is simplicity of initiation. By using a rapid titration rate, leading to a rapid therapeutic gabapentin dose, perhaps there could be an improvement with compliance. Male or female patients, at least 12 years old, with a recent history of partial seizures with or without secondary generalization, were randomized to receive gabapentin (following a blinded placebo period of an undisclosed number of days) as either a Slow initiation (300 mg day 1, 600 mg day 2, then 900 mg/day) or a Rapid initiation (900 mg/day immediately following the placebo lead-in). Starting gabapentin therapy at an initial therapeutic dosage of 900 mg/day is well tolerated by patients with epilepsy and is as safe as initiating with a titration schedule over 3 days. Of the four most common adverse events (somnolence, dizziness, ataxia, fatigue), only one, dizziness, occurred more often in the nontitrated (Rapid initiation) group than in the titrated (Slow initiation) group. Initiation of gabapentin at 900 mg/day is as well tolerated as is a 3-day titration, except for a higher incidence of dizziness.
Many IV antiepileptic drugs administered in emergency situations to patients with prolonged seizu... more Many IV antiepileptic drugs administered in emergency situations to patients with prolonged seizures have serious adverse effects. For this reason, the authors conducted a multicenter, open-label, prospective, dose-escalation study of IV valproate sodium administered to patients with epilepsy at rates of infusion of up to 6 mg/kg/minute and doses of up to 30 mg/kg. Valproate sodium had no clinically significant negative effects on blood pressure and pulse rate and caused only mild-to-moderate, reversible adverse events.
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