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J A French

Publications and source records attributed to J A French.

At least 19 recordsLinked to original sources
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗
PubMed2003

Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures.

BACKGROUND: Pregabalin is an alpha(2)-delta ligand that has anxiolytic, analgesic, and anticonvulsant properties. OBJECTIVE: To establish the efficacy, safety, and tolerability of pregabalin administered twice-daily (BID) without dose titration as adjunctive treatment in patients with partial seizures and to confirm the dose-response relationship. METHODS: This 76-center, double-blind, randomized, placebo-controlled, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Patients with refractory partial seizures on one to three antiepileptic drugs were randomly assigned to one of five treatment groups (placebo or 50, 150, 300, and 600 mg/d pregabalin, all administered BID). Efficacy was assessed using seizure frequency reduction and responder rate (> or =50% seizure reduction from baseline). Pharmacokinetic parameters were estimated. RESULTS: A total of 453 patients were included in the intent-to-treat analysis. The median baseline seizure rate was 10 per month. Seizure frequency reductions from baseline were 7% (placebo; n = 100), 12% (50 mg/d; n = 88), 34% (150 mg/d; n = 86), 44% (300 mg/d; n = 90), and 54% (600 mg/d; n = 89). Responder rates (> or =50% seizure reduction) were 14% (placebo), 15% (50 mg/d), 31% (150 mg/d), 40% (300 mg/d), and 51% (600 mg/d). Discontinuation rates due to adverse events were 5% (placebo), 7% (50 mg/d), 1% (150 mg/d), 14% (300 mg/d), and 24% (600 mg/d). The 150-, 300-, and 600-mg/d pregabalin groups were associated with greater reductions in seizures (p < or = 0.0001) and greater responder rates compared with the placebo group (p < or = 0.006). There was a favorable dose-response trend for both seizure reductions (p < or = 0.0001) and responder rate (p < or = 0.001). CONCLUSION: Adjunctive therapy with pregabalin 150, 300, and 600 mg/d, given in twice-daily doses without titration, is significantly effective and well tolerated in the treatment of patients with partial seizures as demonstrated in patients with refractory partial seizures.

Adolescent↗
PubMed2001

The etiology and diagnosis of status epilepticus.

Status epilepticus (SE) is a common, serious, potentially life-threatening, neurologic emergency characterized by prolonged seizure activity. Generalized convulsive status epilepticus (GCSE) is the most widely recognized form of SE. Direct consequences of convulsive movements from SE can result in injury to the body and brain. Nonconvulsive status epilepticus (NCSE) is underrecognized, with controversy surrounding the consequences and treatment. High mortality rates with GCSE have been noted in the past. New treatments for SE are emerging with new parenteral drug formulations as well as new agents for refractory SE, offering an opportunity to improve outcome. Special drug delivery systems, drug combinations, and neuroprotective agents that prevent the subsequent development of epilepsy may soon emerge as future options for treating SE.

Journal Article↗
PubMed2001

Interactions among paternal behavior, steroid hormones, and parental experience in male marmosets (Callithrix kuhlii).

Male black tufted-ear marmosets (Callithrix kuhlii) contribute to the rearing of their offspring. Here we evaluated predictions of hypotheses suggesting that (1) T and E2 influence infant-care behavior in male marmosets, (2) levels of T and E2 are modulated by paternal experience, and (3) paternal behavior and levels of T and E2 in male marmosets covary with stress. We observed the behavior of marmosets in their family groups following the birth of infants and evaluated urinary concentrations of T, E2, and the stress hormone cortisol (CORT) among fathers before and after the birth of young. Urinary levels of T, E2, and CORT were lower among males who carried infants at high rates than males who carried at low rates, and T and CORT levels were negatively correlated with carrying rates across all males. Males had significantly lower T levels while carrying the second compared to the first litter and slightly lower rates of infant-carrying, possibly due to assistance provided by offspring of the first litter. There were increases in CORT levels of fathers after the birth of the first litter, but decreases in CORT after the birth of the second. Our results suggest a relationship in C. kuhlii between paternal behavior, hormones, and paternal experience. Rates of infant-carrying appear to be linked to hormone levels, and hormone levels in turn are affected by experience caring for young. Our data also suggest that T, E2, and CORT have synergistic influences on infant-carrying behavior or alternatively that associations between T and E2 and rates of infant-carrying are influenced by stress or other glucocorticoid-related variables. Finally, we propose a hypothesis suggesting that experience-related changes in hormones reinforce the commitment of males to successful breeding partnerships.

Animals↗
PubMed2001

Proof of efficacy trials: endpoints.

Seizure frequency data are difficult to work with because they are so variable both between and within patients. Seizures can come in clusters, thereby adding to the variation in seizure frequency. Also, seizure frequency data are non-parametric in nature, making them difficult to analyze by some statistical techniques without transforming them. Therefore, to improve data analysis in proof of efficacy studies, manipulations of seizure frequency are commonly used, such as the proportion of responders above an arbitrary threshold, or the response ratio. Other useful endpoints are time to nth seizure, number of seizure-free days, proportion of seizure-free patients, and assessment of seizure severity using rating scales. The choice of endpoint(s) will depend upon the design of the study.

Anticonvulsants↗
PubMed2001

Postmarketing experience with topiramate and cognition.

Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited central nervous system (CNS) side effects. However, CNS-related treatment-emergent adverse events (TEAEs) often occur in patients receiving AEDs. Topiramate (TPM) is an AED proven to be safe and effective as adjunctive treatment for epilepsy patients with partial seizures. Double-blind, placebo-controlled, multicenter trials demonstrated potential effects on cognition. The P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of 14 epilepsy centers that collaborate on obtaining data about new AEDs and devices, prospectively collected standardized data forms before and during treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS TEAEs with TPM. Our results from 701 treated patients show that cognitive complaints were the most common reason to discontinue TPM. The presence of complaints did have predictive value if the patient would discontinue TPM, although was not specific as to when discontinuation would occur. The spectrum of complaints in our open-label prospective multicenter postmarketing study was similar to those observed in controlled clinical trials. We were unable to demonstrate a specific population, dose titration, or concomitant AED that was at risk to discontinue treatment. We conclude that most patients treated with TPM will continue therapy beyond 6 months. Cognitive complaints and not efficacy reflect the primary reason for discontinuing therapy. Psychomotor slowing was the most common complaint, yet most patients elect to continue treatment, with "better" or "much better" ratings of both seizure and global improvement during treatment.

Adolescent↗
PubMed2001

Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients.

Most of the information on predisposing factors and mortality in status epilepticus (SE) arises from data obtained from patients presenting to the casualty department. However, another population which is frequently seen by consultative neurologists are medically ill patients who develop SE while in hospital. These patients are often notoriously difficult to treat once SE arises. We sought to characterize patients at risk for SE arising when they are hospitalized for other reasons. By doing this, risk factors for developing SE and prognostic indicators might be determined. We retrospectively reviewed records from three urban hospitals in the United States to identify hospitalized patients developing SE over a 1 year period. SE was defined as a clinical seizure lasting 30 minutes or longer, or repeated seizures without recovery. Patients who were admitted in SE or for an epilepsy-related problem, or who were less than 1 year old were excluded from the study. Forty-one patients with in-hospital SE were identified. There were 28 males and 13 females with an age range from 1 to 91 years (mean: 60 years, median: 65 years). The mean interval from hospital admission to the onset of status epilepticus was 26 days. Nineteen (46%) patients had a prior history of either epilepsy or symptomatic seizures, and of these, 10 were inadequately treated as judged by serum anticonvulsant levels at the time SE developed. Focal brain abnormality was present in 26 (63%) patients, the most common of which was stroke (17 patients ). Major metabolic derangements including hypoxia, electrolyte imbalance, hepatic encephalopathy, and sepsis were present in 23 (56%) patients. Eleven (27%) patients were being treated with theophylline preparations at the time SE developed. Mortality in this group of patients with in-hospital SE was 61% (25 deaths), with about one-third dying while in status, and two-thirds dying subsequently in hospital. In this retrospective study, there was no clear relationship between mortality and the duration of SE in this group of patients. In-hospital development of SE is usually related to underlying focal brain abnormality, especially stroke, in combination with systemic metabolic derangement. Prognosis is poor, and appears to be more related to underlying conditions rather than to status duration. More accurate prospective studies are warranted.

Adolescent↗
PubMed2001

The role of new antiepileptic drugs.

For many years, epileptologists had few choices for treating seizures. Within the past 20 years several "new generation" antiepileptic drugs (AEDs) were introduced. The most recent additions include oxcarbazepine, levetiracetam, and zonisamide. New agents have been shown in clinical trials to offer similar efficacy compared with older, more established AEDs, but the new agents offer important improvements in safety. Although clinical trials to specifically measure the efficacy of the new AEDs in treating idiopathic generalized epilepsy are rare, the new agents have demonstrated efficacy in treating generalized tonic-clonic convulsions. Data for treatment of Lennox-Gastaut syndrome indicate a clear effect with lamotrigine or topiramate and possibly some effect with zonisamide and levetiracetam. Studies of juvenile myoclonic epilepsy and absence seizures suggest that zonisamide, lamotrigine, topiramate, and levetiracetam may be effective. Each of the new AEDs is effective in controlling partial seizures. These agents may also be appropriate choices for newly diagnosed patients or those whose conditions are refractory to treatment. In clinical trials, patients who are refractory to treatment are often given escalated doses to gain effect, but higher doses also result in more adverse events and higher withdrawal rates. Generally, the higher the dose, the greater the odds of withdrawal, with the exception of levetiracetam, which is not associated with increased withdrawal rates at high doses. Newly diagnosed patients are likely to be controlled with the first therapy given to them. It is therefore important to select an agent with the best safety, efficacy, and tolerability profile possible.

Anticonvulsants↗
PubMed2001

Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging.

BACKGROUND AND PURPOSE: Interictal hypometabolism has lateralizing value in cases of temporal lobe epilepsy and positive predictive value for seizure-free outcome after surgery to treat epilepsy. Alterations in regional cerebral metabolism can also be inferred from measurements of regional cerebral perfusion. The purpose of this study was to determine the feasibility of detecting cerebral blood flow (CBF) asymmetries in the mesial temporal lobes using continuous arterial spin labeling perfusion MR imaging, which is a noninvasive method for calculating regional CBF. METHODS: Twelve patients with medically refractory temporal lobe epilepsy who underwent preoperative evaluation for temporal lobectomy and 12 normal control participants were studied retrospectively. Absolute and normalized mesial temporal CBF measurements were compared between the patient and control groups. Lateralization based on a perfusion asymmetry index was compared with metabolic ((18)[F]-fluorodeoxyglucose positron emission tomography) and hippocampal volumetric asymmetry indices and with clinical lateralization. RESULTS: Mesial temporal CBF was more asymmetric in patients with temporal lobe epilepsy than in normal control participants, although asymmetric mesial temporal CBF was also found in normal participants, with the left side dominant. Ipsilateral mesial temporal CBF was significantly decreased compared with contralateral mesial temporal CBF in patients with temporal lobe epilepsy. Global CBF measurements were significantly decreased in patients compared with control participants. Asymmetry in mesial temporal blood flow in patients persisted after normalization to global CBF. Lateralization using continuous arterial spin labeling perfusion MR imaging asymmetry index significantly correlated with lateralization based on (18)[F]-fluorodeoxyglucose positron emission tomography hypometabolism, hippocampal volumes, and clinical evaluation. CONCLUSION: Continuous arterial spin labeling perfusion MR imaging can detect interictal asymmetries in mesial temporal lobe perfusion in patients with temporal lobe epilepsy. This technique is readily combined with routine structural assessment and potentially offers an inexpensive and noninvasive means of screening for asymmetries in interictal mesial temporal lobe function.

Adult↗
PubMed2000

Management of epilepsy in adolescents and adults.

Epilepsy is the most common serious neurological disorder affecting an estimated 50 million people worldwide. Particular focus should be placed on a safe diagnosis, seizure and syndrome classification, and choice of pharmacological and surgical options for a range of patient populations with different health-care requirements. Eight new antiepileptic drugs were licensed in the 1990s with more to come. These new drugs along with earlier resective surgery have led to a better outcome for many more people with this condition.

Abnormalities, Drug-Induced↗
PubMed2000

Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is there a link with infant survivorship and maternal behavior?

Recent studies in primates have suggested that pre- and peripartum sex steroid hormones may be important determinants of maternal behavior and motivation, since higher levels of prepartum estrogen are associated with maternal competency and infant survivorship. To test the cross-species generality of this finding, we monitored excreted profiles of estradiol (E(2)), progesterone metabolites (pregnanediol glucuronide; PdG), and E(2):PdG ratios throughout pregnancy in black tufted-ear marmosets (Callithrix kuhlii). Additionally, we wanted to determine the extent to which variability in maternal carrying effort was related to hormonal factors and relative levels of maternal experience. For six females, hormonal profiles were determined by enzyme immunoassay for two pregnancies, one in which infants survived at least 2 weeks postpartum and one in which infants did not survive. Our within-subjects analyses revealed significant differences in mean prepartum E(2) levels for females in the different infant survival conditions. In contrast to previous findings, however, females exhibited significantly higher prepartum E(2) levels when their infants did not survive a minimum of 2 weeks postpartum, relative to when their infants did survive. Maternal carrying effort was also negatively and significantly correlated with prepartum E(2) levels. Unlike previous reports in callitrichid primates, then, our data suggest that high concentrations of prepartum E(2) in callitrichid primates are not necessarily associated with competent maternal behavior and may instead be associated with poor infant survivorship and inadequate maternal care. Further, our results appear to be convergent with research focusing on human mothers and may represent a common underlying mechanism linking prepartum estrogen and postpartum affect and behavior in some primates.

Animals↗
PubMed2000

Antiepileptic drug interactions.

This article reviews the potential interactions of antiepileptic drugs (AEDs) and the pharmacokinetic and pharmacodynamic principles involved. It describes the absorptive and distributive properties of AEDs and the effects on protein binding, hepatic metabolism, and elimination resulting from co-administration of AEDs with food or other drugs. Drug behavior is a function of absorption, metabolism, distribution, and elimination. Administration of either multiple AEDs or a combination of AEDs plus drugs for other conditions can modify any of these physiologic processes, possibly resulting in complex interactions. These may include alterations in the bio-availability and absorption of a drug and changes in half-life and serum level through induction or inhibition of hepatic metabolism. In most cases, increases or decreases in serum concentrations will signal a drug interaction. In other cases, clinically significant drug interactions remain undetected owing to apparently stable serum concentrations. Co-administration of drugs may affect the rate of clearance of one or both drugs. The effect on clearance varies, owing to genetic factors, patient characteristics (age and presence of co-morbidities), and individual responses. AEDs that induce hepatic metabolism can also influence the metabolism of concomitantly administered non-epilepsy medications and can interfere with oral contraceptives, as well as vitamins D and K. Patients with renal insufficiency or advanced age may experience incomplete renal excretion and should receive reduced dosages of drug. Understanding the pharmacokinetics and pharmacodynamic properties of AEDs and the route of metabolism of all competing drugs is important for optimal management of patients with epilepsy and for prevention of avoidable drug interactions.

Anticonvulsants↗
PubMed1999

Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test.

OBJECTIVE: To evaluate changes in arousal and their impact on memory performance during the intracarotid amobarbital test (IAT). METHODS: Along with memory measures, level of arousal was evaluated through clinical ratings and nonverbal self-ratings in epilepsy patients undergoing IAT before anterior temporal lobectomy. RESULTS: Irrespective of seizure focus, left-sided amobarbital injection resulted in decreased objective and subjective arousal more often than right-side injection. Impaired objective arousal was greater when the left hemisphere was injected second, because of the presumed additive effects of systemic amobarbital residual from the first injection. Decreased objective arousal was related to poorer performance on memory testing following left-hemisphere injection. CONCLUSIONS: The IAT, as practiced in most centers, is biased, so patients with right temporal lobe seizure focus are more likely to "pass" the test, whereas patients with left seizure focus are more likely to "fail" the test. The significant impact of changes in arousal on memory testing needs to be considered when using IAT results to select patients for temporal lobectomy.

Adult↗
PubMed1999

Ventricular asystole during vagus nerve stimulation for epilepsy in humans.

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.

Adult↗
PubMed1999

Androgen threshold to activate copulation differs in male rats prenatally exposed to alcohol, stress, or both factors.

Few male rats prenatally exposed to a combination of alcohol and stress copulate spontaneously. This study determined adult sensitivity to testosterone (T) in males prenatally exposed to alcohol, to stress, or to both factors. Sexually naive males were tested with receptive females following castration and implantation of 20-, 30-, or 45-mm Silastic T-filled capsules. Serum T levels provided by these implants were measured. The behavior shown by males exposed only to prenatal alcohol did not differ from untreated control animals at any T dosage. Prenatal stress alone diminished the copulatory potential below control levels only when the intermediate T dosage was provided. Few males exposed to both alcohol and stress copulated under the lowest or the intermediate dose of adult T replacement, but most ejaculated normally when the largest capsule was implanted. The threshold to the sexual behavior-activating-properties of adult T exposure was moderately raised by prenatal stress but was severely affected when prenatal stress was combined with alcohol. We conclude that a diminished sensitivity to androgen in adulthood underlies some copulatory deficits resulting from treatments that alter fetal T levels. Such deficits may be concealed when behavior is evaluated in gonadally intact animals.

Androgens↗