Anticonvulsant Blood Levels Research Articles

Pharmacokinetic changes for newer antiepileptic drugs and seizure control during pregnancy.

ObjectiveTo investigate pharmacokinetic changes in newer antiepileptic drugs (AEDs) and assess seizure frequencies and risk factors of increased seizures during pregnancy in women with epilepsy (WWE).MethodsA total of 56 pregnancies in 53 WWE who received newer antiepileptic drugs (AEDs) were enrolled. Data on seizure activity and types, daily dose, and AEDs blood levels were derived from routine clinical follow‐up. Changes in AEDs clearance were compared between each trimester and nonpregnant baseline. The ratio of AED levels of each trimester to their targets (nonpregnant baseline) concentrations (RTC) was compared between patients with and without an increased seizure. A binary logistic regression was used to investigate the risk factors contributing to seizure worsening during pregnancy.ResultsIncreased clearances of LTG, LEV, and OXC were observed in all trimesters versus nonpregnant baseline. The peak changes in the clearance of LTG (3.42‐fold baseline clearance) (p < 0.001) and LEV (2.78‐fold) (p < 0.001) occurred in the second trimester during pregnancy, followed by oxcarbazepine (2.11‐fold) in the third trimester (p < 0.03). Plasma concentrations of LTG and LEV during pregnancy were significantly decreased compared to baseline levels, except for OXC. However, no significant differences in RTC values were observed between patients with and without seizure worsening. Some risk factors as seizures for the prior nine months could significantly affect seizure frequency during pregnancy.ConclusionWe found substantial changes in the pharmacokinetics of multiple newer AEDs in WWE, reinforcing the need for therapeutic drug monitoring (TDM) during pregnancy. We would encourage at least one monitoring every trimester and probably more frequently for women with poorly seizure control before pregnancy, and AEDs dose adjustment should keep up with clearance changes. In addition, a well‐controlled seizure nine months before pregnancy could lower the risks of seizure during pregnancy, highlighting the importance of pre‐pregnancy counseling and seizure management before pregnancy.

English

A seizure is a brief disturbance of cerebral function, lasting from seconds to a few minutes, caused by an abnormal electrical discharge. Epilepsy is the tendency to have seizures on a chronic, recurrent basis, not resulting from a temporary condition. The term, epilepsy, does not presuppose a cause; there are many causes. Essentially, anything that disturbs the normal functioning of the cerebral cortex can cause seizures, and if this abnormality is enduring, it can result in epilepsy.1 Epilepsy is a common neurological condition with a global prevalence of 1.2 %. Most women with epilepsy who become pregnant or are planning to conceive are recommended to continue taking antiepileptic drugs (AEDs) to minimise seizure recurrence during pregnancy, adverse effects to the fetus, and unintended ill consequences during labour and / or delivery.2,3 The seizure pattern during pregnancy may be influenced by variations in ovarian hormones, blood levels of antiepileptic drugs, and metabolic changes.4 Status epilepticus occurs in only 1 – 2 % of pregnancies,5 and if treated appropriately and aggressively carries a fairly low risk of morbidity and mortality. Structural and metabolic changes may precipitate new-onset seizures during pregnancy. The structural causes include intracranial haemorrhage of multiple types, cerebral venous sinus thrombosis, and ischemic stroke. Metabolic causes include hyperemesis gravidarum; acute hepatitis (due to fatty liver of pregnancy or viral hepatitis); metabolic diseases, such as acute intermittent porphyria; infections, such as malaria; and eclampsia.5 Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach with other specialties such as neurology.6 The threat of seizures during pregnancy and the consequences that they might have on the developing foetus are fundamental reasons for the prescription of daily antiepileptic medication to a pregnant woman with epilepsy (WWE).7 We present an original case of 3 episodes of seizures, of 22-year-old female who was 16 weeks pregnant. This study was approved by Sree Uthradom Thirunal Hospital, Pattom, Trivandrum, Kerala (ethics committee).

Diagnostic evaluation and management of seizures and status epilepticus in children with known epilepsy or new-onset seizures: A retrospective and comparative analysis

ObjectivesThe purpose of this study was to describe and compare the initial management, including clinical/biological investigation and treatment, of new-onset seizures and status epilepticus (SE) in children versus seizures and SE in those with known epilepsy. MethodsThis was a retrospective, single-center, observational study conducted in an urban pediatric hospital in Paris. All patients, aged from 1 month to 18 years, admitted to the pediatric intensive care unit, the high-dependency care unit, and those who required hospitalization in the short-term unit of the emergency department between January 1 and December 31, 2014 for seizures and/or SE were included. ResultsWe analyzed the data of 190 children: new-onset seizures (N=118; group A) versus those with known epilepsy (N=72; group B). At least one diagnostic test was performed on 156 patients (82.1%) (group A, N=104, 88.1%; group B, N=52, 72.2%; P=0.05). In group B, blood levels of antiepileptic drugs were measured in 14 of the 38 patients with SE, of whom six were under dosed. Treatments were: first line, diazepam (group A, 80%; group B, 46%; P<0.001); second line, diazepam (group A, 56%; group B, 34%; P=0.02) or clonazepam (group A, 24%; group B, 46%; P=0.001); third line, phenytoin (group A, 54%; group B, 22%; P<0.001) or clonazepam (group A, 18%; group B, 61%; P<0.001). ConclusionDiagnostic evaluation and treatment should be individualized for children with known epilepsy.

The benefits of antiepileptic drug (AED) blood level monitoring to complement clinical management of people with epilepsy

IntroductionSome argue that there is no evidence to support the use of antiepileptic drug (AED) blood level monitoring when treating people with epilepsy (PWE). This paper identifies how AED monitoring can be invaluable in such treatment. Specific examples(i)Compliance: Antiepileptic drug blood levels often confirm noncompliance rather than adequate seizure control, confirming subtherapeutic levels in PWE attending hospitals due to seizures. Routine monitoring of AED levels may prevent breakthrough seizures by identifying noncompliance and instituting heightened compliance measures before experiencing breakthrough seizures without modifying dosages. For PWE attending hospitals due to seizures, loading with the AED shown to be subtherapeutic may be all that is required.(ii)Cluster seizures and status epilepticus: When using long-acting AEDs to complement benzodiazepines, blood level monitoring confirms that an adequate dosage was given and, if not, a further bolus can be administered with further monitoring. This is particularly useful when using rectal administration of AEDs.(iii)Polypharmacy: Polypharmacy provokes drug interactions in which case AED monitoring helps in differentiating adequate dosing, offending AED with toxicity and free level measuring benefits when total levels are unhelpful.(iv)Generic substitution: Generic AEDs can fluctuate considerably from a parent compound, and even a parent compound, sourced from an alternative supplier, may have altered bioavailability for which blood level monitoring is very useful. ConclusionsWhile therapeutic blood level monitoring is not a substitute for good clinical judgment, it offers a valuable adjunct to patient care.

Prognostic tests and antiepileptic drug withdrawal after epilepsy surgery.

Approximately one in three patients with a successful epilepsy surgery will have seizure recurrence following antiepileptic drugs (AED) withdrawal. The value of postoperative testing for predicting seizure relapse after AED tapering is not clear. The purpose of this study was to review the literature for evidence on the use of postoperative investigations before AED discontinuation after successful epilepsy surgery. We were unable to identify studies on the prognostic value of postoperative magnetic resonance imaging and AED blood levels. The literature review yielded seven studies on the predictive value of electroencephalography. Four studies found no association between interictal discharges (IED) and seizure relapse. These studies suffered from various limitations due to their retrospective design and generally small cohorts. Two of the three studies reporting a positive association were prospective and provided strong evidence of an increased risk of seizure recurrence with presence of postoperative IED in successfully operated patients undergoing AED withdrawal.

Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy

The aims of the study were to characterize the magnitude of clearance changes during pregnancy for multiple antiepileptic drugs (AEDs) and to assess seizure frequency and factors increasing seizure risk in pregnant women with epilepsy. A retrospective analysis was performed for 115 pregnancies in 95 women with epilepsy followed at the Emory Epilepsy Center between 1999 and 2012. Antiepileptic drug blood levels (ABLs) obtained during routine clinical practice were used to calculate AED clearance at multiple points during pregnancy. Antiepileptic drug doses and seizure activity were also recorded. The data were analyzed for changes in clearance and dose across pregnancy and for an association between ABL and changes in seizure frequency. Significant changes in clearance during pregnancy were observed for lamotrigine (p<0.001) and levetiracetam (p<0.006). Average peak clearance increased by 191% for lamotrigine and 207% for levetiracetam from nonpregnant baseline. Marked variance was present across individual women and also across repeat pregnancies in individual women. Despite increased AED dose across most AEDs, seizures increased in 38.4% of patients during pregnancy. Seizure deterioration was significantly more likely in patients with seizures in the 12months prior to conception (p<0.001) and those with localization-related epilepsy (p=0.005). When ABL fell >35% from preconception baseline, seizures worsened significantly during the second trimester when controlling for seizure occurrence in the year prior to conception. Substantial pharmacokinetic changes during pregnancy occur with multiple AEDs and may increase seizure risk. Monitoring of AED serum concentrations with dose adjustment is recommended in pregnant women with epilepsy. Further studies are needed for many AEDs.

The Treatment of Women With Epilepsy

Women with epilepsy and their doctors are often unsure of the implications of the disease and the limitations it causes. There is a major need for counseling. Selective review of the literature as of November 2009. Recommendations on pregnancy and childbearing for women with epilepsy can be found in the guidelines issued by the German Societies of Neurology and Epileptology and by the American Epilepsy Society. Only low-level evidence is available on other relevant questions, including contraception, the influence of hormones on epilepsy, and the influence of antiepileptic drugs on endocrine and bone metabolism, because of a lack of controlled studies. Polycystic ovarian syndrome is more commonly seen in women with epilepsy who take valproate. Antiepileptic drugs that induce CYP3a can diminish the efficacy of oral contraceptives; conversely, oral contraceptives can markedly lower the blood levels of antiepileptic drugs. According to the most recent studies, the risk of congenital malformations and spontaneous abortions is 1% to 2% in the normal population and 3% to 9% in the offspring of women with epilepsy who are taking antiepileptic drugs. Women with epilepsy who want to have children are currently advised to take folic acid prophylactically starting before conception and until the end of the first trimester. New mothers with epilepsy are advised to breastfeed their children. Proper treatment and counseling of women with epilepsy, with due attention to aspects that are specific to women patients, can reduce the limitations to which they are subject in everyday life.

Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet

The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg/l ± 1.0), valproic acid showed a slight but not significant decrease (mean decrease of 6.7 mg/l ± 3.2), 2 weeks after the start of the diet. Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified.

Anti-epileptic drugs: a guide for the non-neurologist

Epilepsy is the most common serious chronic neurological disorder affecting between 0.5% and 1% of Western populations. Most patients take anti-epileptic drugs (AEDs) for years if not decades, and are commonly admitted to hospital with seizures. Many have symptomatic epilepsy, arising as a consequence of another disorder, for example a brain tumour. General practitioners, emergency physicians and most hospital teams (especially general medicine) commonly encounter difficulties surrounding AEDs yet often require assistance from neurology services. This can be difficult when neurology services are not on-site or easily available. This article gives a practical overview of difficulties relating to AEDs and their management, with the focus on problems commonly encountered by non-neurologists. These include the patient who is acutely unwell, pregnant or elderly; AED side effects and drug interactions; status epilepticus and AED blood levels.

Monitoring Antiepileptic Drugs: A Level-Headed Approach

Despite advances in epilepsy therapeutics, some physicians feel uncomfortable with newer antiepileptic drugs (AEDs) due to difficulty in promptly obtaining blood levels to guide medication adjustment, and even when levels for newer AEDs are obtained, many practitioners feel they are not very useful. Lacking confidence in AEDs whose levels that cannot readily or expeditiously be measured, many clinicians share uncertainty about proper use of the newer AEDs and monitoring AED administration. Similarly, some epilepsy patients inflate the importance of AED blood level monitoring, feeling that blood levels falling within traditionally therapeutic ranges are a fail-safe for seizure control, regardless of their compliance or personal behavior aggravating seizure burden, such as poor sleep or use of illicit substances. This review examines the elusive concept of therapeutic AED blood levels and potential uses and abuses of blood level monitoring, reinforcing appropriate uses for blood levels to ensure compliance and adjust for altered AED pharmacokinetics in the context of aging and disease states, pregnancy, or drug interactions.

Manajemen Epilepsi pada Kehamilan

Epilepsy is recognized as the commonest serious neurological disorder in the world. Women with epilepsy experience several gender-related physical and social problems. They constitute high obstetric risk because of reduced fertility, risk of seizures during pregnancy, and complications of pregnancy. Hormonal and other factors can alter the pharmacokinetics of antiepileptic drugs during pregnancy and puerperium. Antenatal exposure to antiepileptic drugs, particularly at higher dosage and in polytherapy, increases the risk of fetal malformation. Recent reports raise the possibility of selective developmental language deficits and neurocognitive deficits with antenatal exposure to antiepileptic drugs. There are concerns regarding the effect of traces of antiepileptic drugs that pass to the infant during breast-feeding. The pre conception management is the cornerstone for epilepsy care in Women with epilepsy. A careful reappraisal of each case should ascertain the diagnosis, the need for continued antiepileptic drugs therapy, selection of appropriate antiepileptic drugs, optimization of the dosage, and prescription of folic acid. During pregnancy, the fetal status needs to be monitored with estimation of serum a-feto-protein and ultrasound screening for malformations. The dosage of antiepileptic drugs can be adjusted according to clinical requirement and blood levels of antiepileptic drugs. Several institutions recommend oral vitamin K toward the end of pregnancy when enzymeinducing. Key Words : epilepsy, pregnancy, management, complication

Mortalidad en niños con epilepsia. Estudio clínico prospectivo

Mortality in patients with epilepsy is higher than the general population, but the data about children is not too extends. OBJECTIVES. To determine the risk of dying in epileptic children, the associated factors and the cause of death, as well as to target the support given to the family.From 1996 to 2002, sixteen children with epilepsy controlled in our centre died. Fifteen of them were included in our research according to a previous protocol. The data was token from our data bank, the clinical file and parents interview.The standard mortality rate was 3.21 (95% CI: 1.48 4.95). The main group had an early onset on their illness. Thirteen children had remote symptomatic epilepsy. Eleven had resistant or catastrophic epilepsy. The EEG was specific for epilepsy in 11 cases. Nine children were receiving politherapy. Eight patients had received three or more therapeutic schemes. Eight had pre mortem therapeutic blood levels of antiepileptic drugs. Ten patients die because of infection and five because of a sudden unexpected death. In one of them the sudden unexpected death was definite and was given in a pregnant teenager with a juvenile myoclonic epilepsy. Other boy died soon after an earthquake. The assistance to the mourning elaboration was useful for the family.This children has a high risk of dying, it is associated to on early onset of severe, active, resistant and catastrophic epilepsy. The entire control of crisis should be the main target of treatment.

Cognitive and Behavioral Effects of Epilepsy Treatment

Summary:Behavior and cognition in patients with epilepsy may be affected by multiple factors including seizure etiology, type, frequency, duration, and severity; cerebral lesions acquired before seizure onset; age at seizure onset; intraictal and interictal physiological dysfunction due to the seizures; structural cerebral damage due to repetitive or prolonged seizures; hereditary factors; psychosocial factors; sequelae of epilepsy surgery; and untoward effects of antiepileptic drugs (AEDs). Although the behavioral and cognitive effects of AEDs are less than the total of other factors in epilepsy, AEDs are of special concern because they are the major therapeutic modality for seizures. The risk of AED cognitive side effects is increased with polypharmacy and at higher dosages and higher AED blood levels. In general, the cognitive effects of AEDs are modest when used in monotherapy with AED blood levels within the standard therapeutic ranges. Further, the cognitive effects of AEDs are offset in part by reduced seizures. However, the cognitive effects of AEDs may be clinically significant. The most common AED cognitive effects include psychomotor slowing, reduced vigilance, and impairments in memory. Phenobarbital (PB) and benzodiazepines (BZDs) possess the most marked adverse cognitive effects. Regarding the other major older AEDs, carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA) have cognitive effects that are similar to each other. In contrast, some of the newer AEDs appear to produce fewer adverse cognitive effects. Gabapentin (GBP) and lamotrigine (LTG) have demonstrated fewer cognitive effects than CBZ and minimal effects compared with placebo. Tiagabine (TGB) and vigabatrin (VGB) also have shown few cognitive effects compared with placebo. Of the new AEDs, topiramate (TPM) appears to have the greatest cognitive side effects, but slow titration during drug initiation reduces these effects. Additional studies are needed to delineate fully the relative effects of all the new AEDs to each other and to the older AEDs. The elderly have increased susceptibility to the cognitive effects of AEDs for both pharmacodynamic and pharmacokinetic reasons. However, only a few studies have examined the cognitive effects of AEDs in the elderly. Although incomplete, the available data reflect a pattern of relative effects similar to those seen in younger adults. Children also may have increased susceptibility because the relatively modest effects of AEDs could be additive over the course of neurodevelopment. Again in children, the cognitive effects of CBZ, PHT, and VPA are comparable, whereas the effects of PB are worse. Unfortunately, there are no studies on the cognitive effects of the new AEDs in children. The effects of AEDs on cognition may have even greater consequences for the children of mothers with epilepsy, who are exposed to AEDs in utero. Animal studies have demonstrated that in utero AED exposure can impair behavioral neurodevelopment at dosages below those required to produce somatic malformations and at clinically relevant blood levels. However, the magnitude and differential effects of in utero AED exposure on neurodevelopment in humans remain uncertain. AEDs may produce positive or negative behavioral alterations (e.g., mood stabilization, irritability/agitation, depression, psychosis). CBZ, GBP, LTG, and VPA have demonstrated positive psychotropic effects. Patients with epilepsy are at increased risk for behavioral disorders, and these AEDs may be particularly useful in such patients. The most severe negative behavioral effects of AEDs occur in a small percentage of patients. However, more subtle adverse behavioral effects are much more common. A patient's perception of his or her quality of life is correlated more with neurotoxicity symptoms and mood than with seizure frequency in the absence of seizure freedom. Even subtle behavioral effects can reduce the patient's quality of life. Thus, the behavioral effects of AEDs should be considered in the choice of AED along with other side effects and efficacy for seizure control.

Pediatric patients with undetectable anticonvulsant blood levels: comparison with compliant patients.

Undetectable anticonvulsant blood levels indicate sustained noncompliance (several consecutive doses missed). We compared 91 consecutive outpatients with epilepsy and undetectable anticonvulsant blood levels to 100 patients seen during the same time period, verified as compliant by acceptable serum levels. We hypothesized that pay status, application for Supplemental Security Income, patient age, history of missed appointments, and functional status would differ between compliant and noncompliant patients. We were surprised to find large differences between clinic and insurance patients and between Caucasian and non-Caucasian patients. The 100 compliant patients included 44 Caucasian and 56 non-Caucasian patients, whereas only 9 of 91 noncompliant patients were Caucasian, and only 9 had insurance, compared to 32 compliant patients. Applications for Supplemental Security Income and history of missed appointments were significantly associated with noncompliance, but patient age, seizure type, and seizure control were not. Uninsured Caucasians were more often compliant than non-Caucasians were. Many noncompliant patients had mild epilepsy, which was reportedly doing well. Race and pay status were closely correlated. Several noncompliant females became pregnant, whereas no compliant patients did. Compliant patients were much more likely to be accompanied by a parent or caretaker on clinic visits than noncompliant patients. Noncompliant patients had at least one acceptable subsequent serum level, although 2 patients with intractable epilepsy had undetectable serum levels on three or more occasions. Noncompliance may respond to discussion and advice. We reviewed 124 episodes of undetectable drug levels in the 91 noncompliant patients. Eighteen of these resulted in hospitalization, but in 25 cases, we were told that there had been no seizures since the preceding visit. Many noncompliant patients have infrequent seizures, even if they take little or no medication. Socioeconomic status influences health, life expectancy, and educational success, but it has been claimed to be irrelevant to compliance and adherence issues in epilepsy. Our data and the experience of other centers with childhood diabetes suggest that socioeconomic, racial, and family factors influence compliance or adherence to treatment for many chronic conditions. Educational efforts and support for parents at the start of anticonvulsant treatment may improve compliance. Uninsured patients missed more appointments and were much more likely to be noncompliant than insured patients. Attention to the special problems of Medicaid and minority children is needed.

Management of antiepileptic drugs following epilepsy surgery: a review.

The favourable impact of surgery for intractable epilepsy on seizures is well documented. However, few studies have determined what changes in antiepileptic drug (AED) therapy occur following surgery. Alterations in AED blood levels in the immediate postoperative period can result in breakthrough seizures. In long term follow-up, one-third to one-half of seizure-free patients after temporal lobectomy, the most common type of epilepsy surgery, still require AED treatment which usually has been reduced from polytherapy to monotherapy. In our study of 93 patients followed two years after temporal lobectomy, polytherapy decreased from 78% before surgery to 14% postoperatively, while medication was discontinued in 44%. Early reduction from polytherapy to monotherapy can often be carried out in the immediate postoperative period but the most appropriate timing of cessation of AED treatment has yet to be determined. Patients undergoing extratemporal resections and other forms of epilepsy surgery associated with less favourable postoperative seizure control may achieve comparatively less reduction in antiepileptic medication. We generally do not recommend stopping AEDs prior to one year after surgery.

Computerised evaluation of cognitive and motor function.

In this paper, we present a clinical study of computerised tracking in the evaluation of cognitive and motor function. We investigate its use in the assessment of effectiveness of antiepileptic drugs (AEDs) as well as in the process of following the progress of Alzheimer's disease (AD). To simplify the experiments, we introduce real-time adaptation of the target speed. In the study with epileptic patients, three result groups are compared: blood levels of AEDs, scores on standard neuropsychological tests, and scores on computerised tracking and reaction time tests. It is found that the computerised tests are repeatable, reliable and sensitive and may therefore be useful in the evaluation of epilepsy treatment. For example, while the blood levels associated with AEDs lie in the therapeutic range, variations in the optimal speed (OS) between 0.9 and 1.1 (expressed in relative units) are recorded. To significantly simplify the protocol for AD patients while preserving its main features, we introduce signal-processing techniques into the data analysis. Local signal property characteristics for AD are found which indicate that the preview tracking of an AD patient is similar to the non-preview tracking of a healthy control. This result is expected since the working memory, which is involved in movement planning, is impaired in AD. In non-preview tracking, healthy control subjects are mostly in tracking mode 1 and have a mean mode duration of 600 ms. In preview tracking, AD patients are mostly in mode 2 with a mean mode duration of 600 ms.

Malformations in offspring of women with epilepsy: a prospective study.

The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors. Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities. The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic-genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients. The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED-related factors are the primary risk factors for an increased incidence of congenital malformations.

Management of Acute Seizure Episodes

Summary: Acute seizures may represent the initial manifestation of epilepsy or isolated events. Urgent treatment of these episodes is indicated to reduce the risk for permanent neurologic damage. Status epilepticus (SE), one form of acute seizure, has an estimated annual incidence of 100,000–150,000 cases per year in the United States. Management of SE focuses on terminating clinical and electrical seizure activity while providing supportive care and identifying the precipitating factors. Physician preference and patient‐related factors may dictate the choice of pharmacologic treatment of SE. However, benzodiazepines, which enter the brain rapidly and offer the opportunity for most rapid seizure cessation, are the foundation for SE management. At our institution, first‐line treatment consists of i.v. lorazepam followed by a long‐acting antiepileptic drug (AED). When i.v. access cannot be attained, high AED blood levels can be rapidly achieved with rectally administered diazepam (DZP). For management of acute repetitive seizures, it is desirable to have an effective drug that can be safely administered by caregivers outside of the hospital setting. Clinical trial data indicate that rectal administration of a prepackaged viscous DZP solution fulfills these criteria. In these studies, rectal DZP gel reduced seizure frequency and recurrence compared to seizure control, improved patient and family quality of life, and was cost‐effective because it reduced the need for emergency and inpatient treatment.

2-17-03 Changes in antiepileptic drugs blood levels following epilepsy surgery

2-17-03 Changes in antiepileptic drugs blood levels following epilepsy surgery

Effects of anticonvulsant therapy on recovery and rehabilitation

Antiepileptic drugs (AEDs) are used in rehabilitation patients with injury to the nervous system for control of clinical seizures, prophylaxis against the development of a seizure disorder, and treatment of secondary mania. Although most AEDs can produce mild cognitive side effects, the benefits of treatment with AEDs in rehabilitation patients with seizure disorders typically outweigh these minor risks, Bromide, phenobarbital, and benzodiazepines may have more severe cognitive side effects than other AEDs. However, there is no convincing evidence of clinically significant differences in cognitive adverse effects among the other established AEDs. Furthermore, cognitive side effects are usually modest with mono therapy and anticonvulsant blood levels within standard therapeutic ranges. With regard to prophylaxis against future seizures, there is no significant data indicating that AED administration can prevent or retard the process of epileptogenesis, Therefore, the use of AEDs to prevent the development of a seizure disorder is not warranted at this time. Finally, although there is little information about the behavioral effects of anticonvulsants in neurological rehabilitation patients, the efficacy of carbamazepine, and perhaps valproate, in the treatment of primary mania suggests that these AEDs may be beneficial in mania secondary to brain injury. The role of AEDs in the treatment of other psychiatric disorders, such as post-traumatic stress disorder and episodic dyscontrol, remains unclear.