Choice Of Antiepileptic Drugs Research Articles

In utero exposure to levetiracetam vs valproate

To compare the cognitive and language development of children born to women with epilepsy (WWE) exposed in utero to levetiracetam (LEV) or sodium valproate (VPA) and control children born to women without epilepsy not taking medication during pregnancy. The children, aged between 36 and 54 months, were recruited from the United Kingdom and assessed using the Griffiths Mental Development Scales and the Reynell Language Development Scale. Maternal demographic and epilepsy information was also collected for use in statistical regression. This is an observational study with researchers not involved in the clinical management of the mothers enrolled. After controlling for confounding variables, children exposed to LEV in utero (n = 53) did not differ from unexposed control children (n = 131) on any scale administered. Children exposed to VPA (n = 44) in utero scored, on average, 15.8 points below children exposed to LEV on measures of gross motor skills (95% confidence interval [CI] -24.5 to -7.1, p < 0.001), 6.4 points below on comprehension language abilities (95% CI -11.0 to -1.8, p = 0.005), and 9.5 points below on expressive language abilities (95% CI -14.7 to -4.4, p < 0.001). The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on women's preferred choice of antiepileptic drug.

Comorbidity between headache and epilepsy in a Chinese epileptic center

Here we investigated the characteristics and prevalence of headaches in patients with epilepsy in a Chinese epileptic center based on the International Classification of Headache Disorders, 2nd edition. We found that 60.14% (667/1109) of patients reported headaches. Headache was less prevalent in males (57.17%) than in females (63.75%). Interictal headaches were present in 34.62% of patients, and 139/1109 (12.53%) patients had interictal migraine, which was a higher percentage than reported in a large population-based study from the same area (9.3%) using the same screening question. In addition, 469 (70.31%) patients had postictal headache, migraine characteristics were present in 73.35% of these patients, and 15.35% also suffered from interictal migraine. Lastly, 8.85% patients had preictal headache. These results confirm that headache is very common in patients with epilepsy. Seizures often trigger postictal headaches with migraine features. The comorbidity of migraines and epilepsy should receive clinical attention, as it may influence antiepileptic drug choice, and the headache may require specific treatment.

The medical and surgical treatment of tumoral seizures: Current and future perspectives

Epilepsy surgery represents the main treatment option for epileptogenic brain tumors. Scalp video-electroencephalography (EEG) and magnetic resonance imaging (MRI) may suffice for defining lesional area and seizure-onset zone in discrete, surgically resectable lesions. The choice of timing for surgery requires a multidisciplinary evaluation, especially in children, when a "wait and see" approach is chosen. Discordant electroclinical and neuroimaging data and an ill-defined epileptogenic lesion require invasive investigations. A multimodal integrated approach may maximize the extent of resection while preserving cerebral function in the eloquent cortex. Radical removal of the tumor is the most important predictor of seizure freedom. Additional predictors include histopathology, age at surgery, duration of epilepsy, and seizure type. Patients with brain tumors are highly vulnerable in relation to the frequent drug-resistance of seizures, the potential interactions between antiepileptic drugs (AEDs) and chemotherapeutic agents (CMTs), and the risk of AED-related cognitive adverse events (24% higher than in the rest of the epilepsy population), in addition to brain damage resulting from tumor itself, surgery, and radiotherapy. No robust, randomized, controlled evidence supports the choice of AEDs for the treatment of seizures in patients with brain tumors. Newer AEDs have limited or no enzyme-inducing profile, prevalent renal excretion, lower plasma protein binding and, consequently, fewer interactions with CMTs. Enzyme-inducing AEDs can lower serum levels of concomitantly administered CMTs. Class I evidence suggests that in patients with brain tumors who do not have a history of seizures, prophylactic use of AEDs is neutral or ineffective.

Pharmacokinetic of Antiepileptic Drugs in Patients with Hepatic or Renal Impairment

Many factors influence choice of antiepileptic drugs (AEDs), including efficacy of the drug for the indication (epilepsy, neuropathic pain, affective disorder, migraine), tolerability, and toxicity. The first-generation AEDs and some newer AEDs are predominately eliminated by hepatic metabolism. Other recent AEDs are eliminated by renal excretion of unchanged drug or a combination of hepatic metabolism and renal excretion. The effect of renal and hepatic disease on the dosing will depend on the fraction of the AED eliminated by hepatic and/or renal excretion, the metabolic isozymes involved, as well as the extent of protein binding, if therapeutic drug monitoring is used. For drugs that are eliminated by renal excretion, methods of estimating creatinine clearance can be used to determine dose adjustments. For drugs eliminated by hepatic metabolism, there are no specific markers of liver function that can be used to provide guidance in dosage adjustments. Based on studies with probe drugs, the hepatic metabolic enzymes are differentially affected depending on the cause and severity of hepatic disease, which can aid in predicting dose adjustment when clinical data are not available. Several AEDs are also associated with laboratory markers of mild hepatic dysfunction and, rarely, more severe hepatic injury. In contrast, the risk of renal injury from AEDs is generally low. In general, co-morbid hepatic or renal diseases influence the decision for the selection of an AED. For some patients dosing changes to their existing AEDs may be appropriate. For others, a change to another AED may be a better option.

Seizures and Epilepsy in Children

Seizures and epilepsy in children are common. They are caused by a variety of causes ranging from genetic to neuro -infections. History and actual observation or/video are very important to differentiate true seizure from non-epileptic event. A correct classification of seizure and epilepsy helps to decide need to treat, choice of anti-epileptic drugs (AED) and prognostication. Except for few seizure types, in majority of seizure types regular AED are started after second confirmed seizure. Goal of treatment is seizure control with minimal side effects and ensuring quality of life. With appropriate mono - therapy, about 70 % patients become seizure free and can be easily treated in community. An orderly approach to classify seizure type, holistic management and timely referral of intractable epilepsy will help in improving care of children with epilepsy.

Pediatric Seizures

On the basis of strong evidence, treatment is highly dependent on the seizure semiology results, electroencephalography (EEG) findings, and origin. • On the basis of moderate evidence and consensus, vigorous use of video EEG recordings and home video cameras should be used to delineate the epileptic syndromes. • On the basis of strong evidence, pediatric epilepsy syndromes have common comorbidities. As a consensus, some pediatric epilepsy centers consider referral to a neuropsychologist to be first-line care in these patients. • On the basis of strong evidence and consensus, antiepileptic drug therapy has its own complications and should be discontinued after an appropriate treatment course. • On the basis of moderate evidence and consensus, uncontrolled seizures put patients at risk for significant morbidity and mortality.

Prise en charge symptomatique des métastases cérébrales

Indications and choice of antiepileptic drugs (AED), treatments for cerebral edema and prophylactic and curative treatments of thromboembolic complications of brain metastasis are discussed.

MANAGEMENT OF ACUTE SYMPTOMATIC SEIZURES: OUTLINE OF CURRENT PRACTICE

Acute symptomatic seizures (ASS) occur at the time or in close temporal association with a documented systemic or brain insult and are a common cause for seeking an emergency neurological...

Epilepsy in elderly patients: focus on treatment

Epilepsy is a disorder widely distributed across all age groups, although its incidence and prevalence favours elderly patients. In this population the development of epilepsy is mainlyrelated to other brain disorders that facilitate the occurrence of late seizures, mostly of focal onset. Apart from the difficulties faced in current practice with the appropriate diagnosis of the epileptic nature of the episodes, old subjects require an individualised drug treatment, tailored on their characteristics, such as comorbidity, polytherapy, age-associated biological impairment and compliance. Among the various antiepileptic drugs available for the treatment of epilepsy, rational selection and combination of drugs should drive both initiation and maintenance of the treatment. Choice of antiepileptic drugs should first focus on avoidance of adverse effects and potential drug interactions. The pharmacological control of seizures is usually favourable at this age, with a good prognosis. However, alternative therapeutic options should be considered as soon as drug-response is unsatisfactory.

Recent Innovations in the Management of Low-Grade Gliomas

Advancement in the understanding of biologic mechanisms of low-grade glioma pathophysiology has allowed the modern era of patient-specific genetic profiling, molecular biology, and neuroimaging to design new methods of surgery, radiation, and chemotherapy in hopes of preventing malignant transformation and improving outcomes. Recent innovations in the understanding of MGMT promoter methylation, IDH1 and IDH2 mutations, temozolomide chemotherapy, vascular monoclonal antibody treatment, use of radiation therapy, choice of antiepileptic drugs, surgical resection, and neuroimaging of low-grade gliomas are reviewed.

High concentration of immunoglobulin A is associated with temporal lobe epilepsy

Dysfunction of immunoglobulins (Igs) has been detected in association with antiepileptic drugs (AEDs) and in newly diagnosed epilepsy patients. The aim of this study was to evaluate the effect of clinical features and the current or past use of AEDs on serum Ig concentrations in a well-examined group of patients with refractory epilepsy. Using a nephelometric method, concentrations of IgA, IgG and IgM were analyzed in the sera of 257 patients with refractory epilepsy, 15 patients with controlled epilepsy and 584 healthy control subjects. A low IgA concentration was found in 8.8% of the patients with epilepsy compared with 1.9% of the control subjects. High concentrations of IgA were associated with temporal lobe epilepsy (TLE) compared with other epilepsy types (p=0.042). The high concentrations of IgA (p=0.042), low concentrations of IgG (p=0.002), and high concentrations of IgG (p=0.008) were also associated with autoimmune diseases. The use of lamotrigine, nitrazepam, oxcarbazepine, topiramate and valproic acid was associated with alterations in Ig concentrations. Current use of topiramate was associated with high serum IgG and IgM concentrations (OR 10.39; 95% CI: 3.08-35.04 and OR 7.02; 95% CI: 1.25-39.55, respectively). The finding of high serum IgA concentration in patients with TLE strengthens the previously found association of immunological activity in the epileptic temporal lobe rather than other brain regions. The newly observed immunological effects of topiramate are important to proper AED choice in patients with refractory epilepsy.

Lamotrigine use in pregnancy

Lamotrigine is a sodium-channel-modulating, antiepileptic drug (AED), which was approved in the USA in 1994 for use in partial-onset seizures. It was ultimately approved for monotherapy in 1998. Lamotrigine has gained widespread use in the USA as both an immediate and an extended-release agent. Lamotrigine is effective against a broad spectrum of seizure types and has a favorable metabolic profile, with few but significant drug interactions. Pregnancy registries in several countries have demonstrated that AED use in women with epilepsy is associated with an increased risk of fetal malformations, if the infant is exposed during the period of organogenesis. In addition, new evidence demonstrates that AEDs may affect the intellectual development of a child, as measured up until the age of 3 years. This information has made the choice of an anticonvulsant for a woman who might become pregnant significantly more important. Pregnancy registries have consistently demonstrated lamotrigine to be among the safest medications for a developing fetus, both in terms of fetal malformations and postpartum cognitive development. These findings make lamotrigine probably the first choice of AED for women wishing to become pregnant and for whom the medication is appropriate.

Economic evaluation of anti-epileptic drug therapies with specific focus on teratogenic outcomes

Background:Anti-epileptic drugs are known to be teratogenic, yet many women do need to continue the anti-epileptic drug use during pregnancy.Objectives:To perform an economic evaluation of the anti-epileptic drug choice in young women who potentially wish to become pregnant. In particular, to estimate the impact of teratogenicity on the costs per quality adjusted life year (QALY).Methods:A decision-tree model is used to calculate the costs per QALY, taking into account the malformation risk in offspring due to the exposure to carbamazepine, lamotrigine or valproic acid, based on the European birth cohort of 2007. Probabilistic sensitivity analyses were performed using Monte Carlo simulation.Results:Valproic acid is dominated by carbamazepine after rank ordering on costs. The incremental cost-effectiveness of lamotrigine vs carbamazepine was estimated at €175,534 per QALY. Although valproic acid was dominated by carbamazepine in terms of costs and related effects, it is clinically relevant to compare lamotrigine with valproic acid. In particular, treatment options are dependent on several individual and clinical characteristics and these agents are therefore not always considered as interchangeable for all specified populations. The incremental cost-effectiveness for lamotrigine vs valproic acid was estimated at €13,370 per QALY. With assuming a willingness to pay threshold of €50,000 per QALY, results from the probabilistic analysis resulted in an acceptance level for lamotrigine vs carbamazepine and lamotrigine vs valproic acid of 4% and 99%, respectively.Conclusion:Based on epidemiological data it is advised to whenever possible avoid valproic acid during pregnancy. Both carbamazepine and lamotrigine are estimated to be cost-effective treatment options vs valproic acid if focused on teratogenicity.

Brain tumor-related epilepsy.

In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures.In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient’s psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness.

Patients with brain tumor-related epilepsy

Patients with brain tumor-related epilepsy (BTRE) present a complex therapeutic profile and require a unique and multidisciplinary approach. They, in fact, must face two different pathologies at the same time, brain tumor and epilepsy. Therefore, it is necessary to develop a customized treatment plan for each individual with BTRE. This requires a vision of patient management concerned not only with medical therapies related to the oncological disease and to the correct choice of antiepileptic therapies but also with emotional and psychological support for the individual and his/her family. The choice of antiepileptic drugs is challenging for these patients because BTRE is often drug-resistant, has a strong impact on the quality of life, and weighs heavily on public health expenditures. In brain tumor patients, the presence of epilepsy is considered the most important risk factor for long-term disability. The problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control also has a significant impact on the patient's psychological and relational sphere.

A Review of the Use of Antiepileptic Drugs in High-Grade Central Nervous System Tumors

Seizures are a common complication in patients with central nervous system (CNS) tumors. Optimal management is unclear with no defined guidelines and pharmacological management poses many controversies. Due to a hypothesized lack of consistency, we aimed to retrospectively review seizure management in patients with high-grade CNS tumors in our institution. The medical records of patients with high-grade CNS tumors referred to the specialist palliative medicine service in our institution from January-June 2008 were retrospectively reviewed. Seizure incidence, antiepileptic drug (AED) choice, neurology input, medication interactions, and appropriate drug level monitoring were assessed. Twenty-seven patients were included for analysis. Fifteen (56%) were female. The mean age was 58.8 years (range 31-82 years). Three (11%) patients presented with seizures and 8 (30%) developed seizures subsequently. Eight (73% of those with seizures) were on monotherapy AED. Six different agents were used as first-line agents. Phenytoin was the most common AED used (n = 4). Three (27%) patients were on combination AEDs. Five (45.5%) patients had been seen by neurology and 6 (54.5%) had appropriate drug level monitoring performed. Six (55%) patients had potential AED-non-AED interactions. None of the patients had instructions documented in the clinical notes against driving. Seizure management in patients with CNS tumors is not consistent and remains very much a neglected area. Appropriate choice of AED is crucial. Physicians should be aware of potential drug interactions. Ownership and regular follow-up of this group is required to ensure optimum patient management.

042 A critical analysis of studies of antiepileptic drugs (AEDs) and pregnancy. Maternal safety is neglected

Guidelines for AEDs during pregnancy emphasise dangers of polytherapy and sodium valproate. I evaluate 1651 articles on AEDs and pregnancy since 1970, identified through a PubMed search. All studies are...

Neuroimaging observations in a cohort of elderly manifesting with new onset seizures: Experience from a university hospital

Background:The occurrence of epilepsy is higher among elderly patients. The clinical manifestations of seizures, causes of epilepsy, and choice of anti-epileptic drugs (AEDs) are different in elderly people with epilepsy compared to the young.Aim:To evaluate the imaging (CT/MRI) observations in elderly patients manifesting with new-onset seizures.Materials and Methods:Two hundred and one elderly patients with new onset seizures, >60 years (age: 68.0 ± 7.5 years; M:F = 1.8:1) from Jan’ 07 to Jan’ 09, were prospectively recruited. Observations of cranial CT scan (n = 201) and MR imaging (n = 43) were analyzed.Results:The type of seizures included: Simple partial (42%), generalized tonic-clonic (30.3%), and complex partial (27.4%). The pattern of epilepsy syndromes were acute symptomatic (42.3%), remote symptomatic (18.4%), cryptogenic (37.8%), and idiopathic (1.5%). Seizures were controlled with monotherapy in 85%. The CT scan (n = 201) revealed cerebral atrophy (139), mild (79), moderate (43), and severe (18); focal lesions (98), infarcts (45), hemorrhages (18), granuloma (16), tumor (15) and gliosis (4), and hemispheric atrophy (1), white matter changes (75) and diffuse edema (21). An MRI (n = 43) showed variable degree of cerebral atrophy (31); white matter changes (20); focal cerebral lesions (24); - infarct (7); intracranial hemorrhage (6); granuloma (5); tumor (6); gliosis (1); hemispheric atrophy (1); and prominent Virchow-Robin spaces (7); and UBOs (12). Patients with focal lesions in neuroimaging more often had partial seizures, symptomatic epilepsy, past stroke, focal deficit, absence of diffuse atrophy, focal EEG slowing, abnormal CSF, seizure recurrence at follow-up (P < 0.05).Conclusions:Brain imaging observations in elderly patients with new-onset seizures revealed underlying symptomatic nature, hence the etiology and thereby assisted in deciding the specific therapy.

The actual choice of anti-epileptic drugs in patients with traumatic brain injury

The actual choice of anti-epileptic drugs in patients with traumatic brain injury

Lecture: profile of risks and benefits of new antiepileptic drugs in brain tumor-related epilepsy

In patients with brain tumor, seizures are the onset symptom in 20-40% of the patients, while a further 20-45% of the patients will present them during the course of the disease. These data are important when considering the choice of antiepileptic drugs for this particular patient population, because brain tumor-related epilepsy (BTRE) is often drug resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures. In brain tumor patients, the presence of epilepsy is considered as the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient's psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, and zonisamide are preferred, because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered as a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each patient with BTRE, whose goals are complete seizure control, minimal or no side effects, and elimination of cognitive impairment and/or psychosocial problems.