Page Pennell - Academia.edu (original) (raw)

Papers by Page Pennell

Epilepsy currents / American Epilepsy Society

Children born to mothers taking antiepileptic drugs (AEDs) are at increased risk for findings of ... more Children born to mothers taking antiepileptic drugs (AEDs) are at increased risk for findings of fetal anticonvulsant syndrome. Accepted treatment paradigms to minimize fetal risks include use of AED monotherapy and folic acid supplementation. However, as data are acquired from several ongoing pregnancy registries, differential risks among the various AED monotherapy regimens are being defined, further improving fetal outcomes.

Steroids, 2015

Analytical techniques used to quantify neurosteroids in biological samples are often compromised ... more Analytical techniques used to quantify neurosteroids in biological samples are often compromised by non-specificity and limited dynamic range which can result in erroneous results. A relatively rapid and inexpensive gas chromatography-mass spectrometry (GC-MS) was developed to simultaneously measure nine neurosteroids, including allopregnanolone, estradiol, and progesterone, as well as 25-hydroxy-vitamin D3 in plasma samples collected from adult women subjects during and after pregnancy. Sample preparation involved solid-phase extraction and derivatization, followed by automated injection on a GC equipped with a mass selective detector (MSD) operated in single ion monitoring (SIM) mode to yield a run time of less than 11min. Method detection limits for all neurosteroids ranged from 30 to 200pg/mL (parts per trillion), with coefficients of variation that ranged from 3% to 5% based on intra-assay comparisons run in triplicate. Although concentrations of estradiol measured by chemilumi...

International review of neurobiology, 2008

The ideal management of women with epilepsy during pregnancy involves achieving an optimal balanc... more The ideal management of women with epilepsy during pregnancy involves achieving an optimal balance between minimizing fetal exposure to the deleterious influences of both antiepileptic drugs (AEDs) and of seizures. Women with increased seizures during pregnancy tend to have subtherapeutic AED concentrations. Multiple physiological changes during pregnancy influence drug disposition, including increased volume of distribution, increased renal elimination, altered hepatic enzyme activity, and a decline in plasma protein concentrations. Many of the AEDs are characterized by significant increases in clearance during pregnancy. Studies performed thus far provide convincing findings for significant increases in the clearance of lamotrigine and phenytoin during pregnancy; other studies support that phenobarbital, oxcarbazepine, and levetiracetam clearances also most likely increase during pregnancy. Therapeutic drug monitoring of lamotrigine with adjustment of dosages during pregnancy to m...

Epilepsy currents / American Epilepsy Society

Epilepsia 2005;46(5):775-777 PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at bir... more Epilepsia 2005;46(5):775-777 PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at birth, during lactation, and in the nursed infant.

Neurology, 2003

The ideal management of women with epilepsy during pregnancy and the postpartum period involves a... more The ideal management of women with epilepsy during pregnancy and the postpartum period involves achieving an optimal balance between minimizing fetal and neonatal exposure to the deleterious influences both of antiepileptic drugs (AEDs) and of seizures. Women with increased seizures during pregnancy tend to have subtherapeutic AED concentrations. Multiple physiologic changes during pregnancy influence drug disposition, including increased volume of distribution, increased renal elimination, altered hepatic enzyme activity, and a decline in plasma protein concentrations. Noncompliance can also be a major factor. The majority of AEDs are characterized by significant increases in clearance during pregnancy. Lamotrigine (LTG) clearance markedly increases throughout pregnancy, to an extent greater than with the older AEDs. Studies during and after birth in mothers taking the older AEDs indicate extensive transplacental transfer and low to moderate excretion into breast milk. Limited stud...

Epilepsia, 1994

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated ... more We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T, signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with "cryptogenic" temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T, Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T, intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.

Neurology, Jan 10, 2003

The great majority of women with epilepsy who become pregnant have normal pregnancies and healthy... more The great majority of women with epilepsy who become pregnant have normal pregnancies and healthy infants. However, in utero exposure to antiepileptic drugs (AEDs) can put infants of women with epilepsy at increased risk for a variety of abnormalities, including intrauterine growth retardation, minor anomalies, major congenital malformations, microcephaly, and cognitive dysfunction. Various combinations of these findings can occur in an individual infant and are referred to as the fetal anticonvulsant syndrome (FAS). The most common major malformations are cleft lip/palate, heart defects, neural tube defects, and urogenital defects. Although AEDs have teratogenic risks, withdrawal of all AEDs before pregnancy is not a realistic option for many women with epilepsy. The results of several studies indicate that AED monotherapy reduces the risk for development of FAS compared with polytherapy exposure in utero. Current treatment guidelines advise use of AED monotherapy when possible and...

Seizure, 2014

Intravenous (IV) formulations are useful when treating patients where oral administration is not ... more Intravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients. Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation). No significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation. Our results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

Annals of Clinical and Translational Neurology, 2014

Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of... more Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods: Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results: A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation: The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery.

Objective: To reassess the evidence for management issues related to the care of women with epile... more Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. Methods: Systematic review of relevant articles published between January 1985 and June 2007. Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possi- ble compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the develop- ment of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to mono- therapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive out- comes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cogni- tive outcomes. Neonates of WWE taking AEDs probably have an in...

Seminars in Neurology, 2002

Pregnancy in women with epilepsy is associated with increased obstetric risks and increased adver... more Pregnancy in women with epilepsy is associated with increased obstetric risks and increased adverse neonatal outcomes. Prior to conception, folic acid should be administered and the antiepileptic drug (AED) regimen should be optimized. Effective control of maternal seizures with the least risk to the fetus is the goal, preferably using AED monotherapy. Periodic monitoring of total and free AED levels is recommended. The "fetal anticonvulsant syndrome" has been described with all of the AEDs and includes major malformations, minor anomalies, microcephaly, cognitive impairment, intrauterine growth retardation, and infant mortality. The most common major malformations are cleft lip/palate, heart defects, and neural tube defects. Prenatal screening should be offered. Supplemental vitamin K 1 should be given to the mother and newborn to prevent neonatal hemorrhagic disorder. Careful planning and management of any pregnancy in women with epilepsy are essential to increase the likelihood of a healthy outcome for the mother and infant.

Seizure, 2013

Patients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a... more Patients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a clear indication. We compared the percentage of patients with spontaneous ICH who had seizures at onset or during hospitalization, and examined empiric use of antiepileptic drugs (AEDs) in these patients in 2 cohorts 10 years apart. Using a clinical data registry at a tertiary care adult hospital, we retrospectively selected admissions for spontaneous ICH between 1/1/99-12/31/00 (Cohort A, n=30) and 1/1/09-12/31/10 (Cohort B, n=108). Clinical, neurophysiological and radiological data were collected in both cohorts. In Cohorts A and B respectively, AEDs were started in 53.3% and 50.0%, and continued on discharge in 50.0% and 20.4% of patients; 86.6% and 59.1% of patients discharged on AEDs did not have a clinical/electrographic seizure or epileptiform EEG findings. Seizures occurred in 6.6% and 13.0% in Cohorts A and B respectively. The presence of a seizure at presentation (p=0.01) and during hospitalization (p=0.02) were predictors for continuing AED on discharge. In both cohorts, a significant number of patients were discharged on AEDs without a clear indication, though there is a change in practice between the two cohorts.

PEDIATRICS, 2008

The information on lamotrigine in breastfeeding is very limited. There are no established infant-... more The information on lamotrigine in breastfeeding is very limited. There are no established infant-monitoring guidelines and limited methodologic rigor in previous studies.

New England Journal of Medicine, 2009

BACKGROUND-Fetal exposure of animals to antiepileptic drugs at doses lower than those required to... more BACKGROUND-Fetal exposure of animals to antiepileptic drugs at doses lower than those required to produce congenital malformations can produce cognitive and behavioral abnormalities, but cognitive effects of fetal exposure of humans to antiepileptic drugs are uncertain.

Neuron, 2001

Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes... more Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes before clinical seizure onset. We analyzed continuous 3- to 14-day intracranial EEG recordings from five patients with mesial temporal lobe epilepsy obtained during evaluation for epilepsy surgery. We found localized quantitative EEG changes identifying prolonged bursts of complex epileptiform discharges that became more prevalent 7 hr before seizures and highly localized subclinical seizure-like activity that became more frequent 2 hr prior to seizure onset. Accumulated energy increased in the 50 min before seizure onset, compared to baseline. These observations, from a small number of patients, suggest that epileptic seizures may begin as a cascade of electrophysiological events that evolve over hours and that quantitative measures of preseizure electrical activity could possibly be used to predict seizures far in advance of clinical onset.

Neurologic Clinics, 2009

The interactions between hormones, epilepsy, and the medications used to treat epilepsy are compl... more The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis. Common symptoms include sexual dysfunction, decreased fertility, premature menopause, and polycystic ovarian syndrome. Antiepileptic drugs and hormones have a bidirectional interaction, with a decrease in the efficacy of hormonal contraceptive agents with some AEDs and a decrease in the concentration and efficacy of other AEDs with hormonal contraceptives. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this knowledge can be used to develop hormonal strategies to improve seizure control in people with epilepsy.

Neurologic Clinics, 2004

More than one million women who have epilepsy in the United States are in their active reproducti... more More than one million women who have epilepsy in the United States are in their active reproductive years and give birth to more than 24,000 infants each year. It is estimated, however, that the total number of children in the United States exposed in utero to antiepileptic drugs (AEDs) is nearly two times that amount with the emergence of AED use for other illnesses, including headache, chronic pain, and mood disorders [1], and AEDs are one of the most frequent teratogen exposures for all pregnancies [2,3]. Many of the principles about AED use during pregnancy outlined in this article can be extrapolated to women who have any disorder treated with these agents.

Epilepsy currents / American Epilepsy Society

Children born to mothers taking antiepileptic drugs (AEDs) are at increased risk for findings of ... more Children born to mothers taking antiepileptic drugs (AEDs) are at increased risk for findings of fetal anticonvulsant syndrome. Accepted treatment paradigms to minimize fetal risks include use of AED monotherapy and folic acid supplementation. However, as data are acquired from several ongoing pregnancy registries, differential risks among the various AED monotherapy regimens are being defined, further improving fetal outcomes.

Steroids, 2015

Analytical techniques used to quantify neurosteroids in biological samples are often compromised ... more Analytical techniques used to quantify neurosteroids in biological samples are often compromised by non-specificity and limited dynamic range which can result in erroneous results. A relatively rapid and inexpensive gas chromatography-mass spectrometry (GC-MS) was developed to simultaneously measure nine neurosteroids, including allopregnanolone, estradiol, and progesterone, as well as 25-hydroxy-vitamin D3 in plasma samples collected from adult women subjects during and after pregnancy. Sample preparation involved solid-phase extraction and derivatization, followed by automated injection on a GC equipped with a mass selective detector (MSD) operated in single ion monitoring (SIM) mode to yield a run time of less than 11min. Method detection limits for all neurosteroids ranged from 30 to 200pg/mL (parts per trillion), with coefficients of variation that ranged from 3% to 5% based on intra-assay comparisons run in triplicate. Although concentrations of estradiol measured by chemilumi...

International review of neurobiology, 2008

The ideal management of women with epilepsy during pregnancy involves achieving an optimal balanc... more The ideal management of women with epilepsy during pregnancy involves achieving an optimal balance between minimizing fetal exposure to the deleterious influences of both antiepileptic drugs (AEDs) and of seizures. Women with increased seizures during pregnancy tend to have subtherapeutic AED concentrations. Multiple physiological changes during pregnancy influence drug disposition, including increased volume of distribution, increased renal elimination, altered hepatic enzyme activity, and a decline in plasma protein concentrations. Many of the AEDs are characterized by significant increases in clearance during pregnancy. Studies performed thus far provide convincing findings for significant increases in the clearance of lamotrigine and phenytoin during pregnancy; other studies support that phenobarbital, oxcarbazepine, and levetiracetam clearances also most likely increase during pregnancy. Therapeutic drug monitoring of lamotrigine with adjustment of dosages during pregnancy to m...

Epilepsy currents / American Epilepsy Society

Epilepsia 2005;46(5):775-777 PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at bir... more Epilepsia 2005;46(5):775-777 PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at birth, during lactation, and in the nursed infant.

Neurology, 2003

The ideal management of women with epilepsy during pregnancy and the postpartum period involves a... more The ideal management of women with epilepsy during pregnancy and the postpartum period involves achieving an optimal balance between minimizing fetal and neonatal exposure to the deleterious influences both of antiepileptic drugs (AEDs) and of seizures. Women with increased seizures during pregnancy tend to have subtherapeutic AED concentrations. Multiple physiologic changes during pregnancy influence drug disposition, including increased volume of distribution, increased renal elimination, altered hepatic enzyme activity, and a decline in plasma protein concentrations. Noncompliance can also be a major factor. The majority of AEDs are characterized by significant increases in clearance during pregnancy. Lamotrigine (LTG) clearance markedly increases throughout pregnancy, to an extent greater than with the older AEDs. Studies during and after birth in mothers taking the older AEDs indicate extensive transplacental transfer and low to moderate excretion into breast milk. Limited stud...

Epilepsia, 1994

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated ... more We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T, signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with "cryptogenic" temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T, Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T, intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.

Neurology, Jan 10, 2003

The great majority of women with epilepsy who become pregnant have normal pregnancies and healthy... more The great majority of women with epilepsy who become pregnant have normal pregnancies and healthy infants. However, in utero exposure to antiepileptic drugs (AEDs) can put infants of women with epilepsy at increased risk for a variety of abnormalities, including intrauterine growth retardation, minor anomalies, major congenital malformations, microcephaly, and cognitive dysfunction. Various combinations of these findings can occur in an individual infant and are referred to as the fetal anticonvulsant syndrome (FAS). The most common major malformations are cleft lip/palate, heart defects, neural tube defects, and urogenital defects. Although AEDs have teratogenic risks, withdrawal of all AEDs before pregnancy is not a realistic option for many women with epilepsy. The results of several studies indicate that AED monotherapy reduces the risk for development of FAS compared with polytherapy exposure in utero. Current treatment guidelines advise use of AED monotherapy when possible and...

Seizure, 2014

Intravenous (IV) formulations are useful when treating patients where oral administration is not ... more Intravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients. Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation). No significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation. Our results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

Annals of Clinical and Translational Neurology, 2014

Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of... more Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods: Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results: A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation: The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery.

Objective: To reassess the evidence for management issues related to the care of women with epile... more Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. Methods: Systematic review of relevant articles published between January 1985 and June 2007. Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possi- ble compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the develop- ment of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to mono- therapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive out- comes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cogni- tive outcomes. Neonates of WWE taking AEDs probably have an in...

Seminars in Neurology, 2002

Pregnancy in women with epilepsy is associated with increased obstetric risks and increased adver... more Pregnancy in women with epilepsy is associated with increased obstetric risks and increased adverse neonatal outcomes. Prior to conception, folic acid should be administered and the antiepileptic drug (AED) regimen should be optimized. Effective control of maternal seizures with the least risk to the fetus is the goal, preferably using AED monotherapy. Periodic monitoring of total and free AED levels is recommended. The "fetal anticonvulsant syndrome" has been described with all of the AEDs and includes major malformations, minor anomalies, microcephaly, cognitive impairment, intrauterine growth retardation, and infant mortality. The most common major malformations are cleft lip/palate, heart defects, and neural tube defects. Prenatal screening should be offered. Supplemental vitamin K 1 should be given to the mother and newborn to prevent neonatal hemorrhagic disorder. Careful planning and management of any pregnancy in women with epilepsy are essential to increase the likelihood of a healthy outcome for the mother and infant.

Seizure, 2013

Patients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a... more Patients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a clear indication. We compared the percentage of patients with spontaneous ICH who had seizures at onset or during hospitalization, and examined empiric use of antiepileptic drugs (AEDs) in these patients in 2 cohorts 10 years apart. Using a clinical data registry at a tertiary care adult hospital, we retrospectively selected admissions for spontaneous ICH between 1/1/99-12/31/00 (Cohort A, n=30) and 1/1/09-12/31/10 (Cohort B, n=108). Clinical, neurophysiological and radiological data were collected in both cohorts. In Cohorts A and B respectively, AEDs were started in 53.3% and 50.0%, and continued on discharge in 50.0% and 20.4% of patients; 86.6% and 59.1% of patients discharged on AEDs did not have a clinical/electrographic seizure or epileptiform EEG findings. Seizures occurred in 6.6% and 13.0% in Cohorts A and B respectively. The presence of a seizure at presentation (p=0.01) and during hospitalization (p=0.02) were predictors for continuing AED on discharge. In both cohorts, a significant number of patients were discharged on AEDs without a clear indication, though there is a change in practice between the two cohorts.

PEDIATRICS, 2008

The information on lamotrigine in breastfeeding is very limited. There are no established infant-... more The information on lamotrigine in breastfeeding is very limited. There are no established infant-monitoring guidelines and limited methodologic rigor in previous studies.

New England Journal of Medicine, 2009

BACKGROUND-Fetal exposure of animals to antiepileptic drugs at doses lower than those required to... more BACKGROUND-Fetal exposure of animals to antiepileptic drugs at doses lower than those required to produce congenital malformations can produce cognitive and behavioral abnormalities, but cognitive effects of fetal exposure of humans to antiepileptic drugs are uncertain.

Neuron, 2001

Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes... more Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes before clinical seizure onset. We analyzed continuous 3- to 14-day intracranial EEG recordings from five patients with mesial temporal lobe epilepsy obtained during evaluation for epilepsy surgery. We found localized quantitative EEG changes identifying prolonged bursts of complex epileptiform discharges that became more prevalent 7 hr before seizures and highly localized subclinical seizure-like activity that became more frequent 2 hr prior to seizure onset. Accumulated energy increased in the 50 min before seizure onset, compared to baseline. These observations, from a small number of patients, suggest that epileptic seizures may begin as a cascade of electrophysiological events that evolve over hours and that quantitative measures of preseizure electrical activity could possibly be used to predict seizures far in advance of clinical onset.

Neurologic Clinics, 2009

The interactions between hormones, epilepsy, and the medications used to treat epilepsy are compl... more The interactions between hormones, epilepsy, and the medications used to treat epilepsy are complex, with tridirectional interactions which affect both men and women in various ways. Abnormalities of baseline endocrine status occur more commonly in people with epilepsy, and are most often described for the sex steroid hormone axis. Common symptoms include sexual dysfunction, decreased fertility, premature menopause, and polycystic ovarian syndrome. Antiepileptic drugs and hormones have a bidirectional interaction, with a decrease in the efficacy of hormonal contraceptive agents with some AEDs and a decrease in the concentration and efficacy of other AEDs with hormonal contraceptives. Endogenous hormones can influence seizure severity and frequency, resulting in catamenial patterns of epilepsy. However, this knowledge can be used to develop hormonal strategies to improve seizure control in people with epilepsy.

Neurologic Clinics, 2004

More than one million women who have epilepsy in the United States are in their active reproducti... more More than one million women who have epilepsy in the United States are in their active reproductive years and give birth to more than 24,000 infants each year. It is estimated, however, that the total number of children in the United States exposed in utero to antiepileptic drugs (AEDs) is nearly two times that amount with the emergence of AED use for other illnesses, including headache, chronic pain, and mood disorders [1], and AEDs are one of the most frequent teratogen exposures for all pregnancies [2,3]. Many of the principles about AED use during pregnancy outlined in this article can be extrapolated to women who have any disorder treated with these agents.