Adult and pediatric physiologically-based biopharmaceutics modeling to explain lamotrigine immediate release absorption process.

Physiologically-based biopharmaceutics modeling (PBBM) has potential to accelerate the development of new drug and formulations. An important application of PBBM is for special populations such as pediatrics that have pharmacokinetics dependent on the maturation process. Lamotrigine (LTG) is a Biopharmaceutics Classification System (BCS) II drug and is widely prescribed. Therefore, the goal of this study was to assess the biopharmaceutics risk of the low-soluble drug LTG when the ontogeny on gastrointestinal tract (GIT) physiological parameters are considered. An oral physiologically-based pharmacokinetic model and a PBBM were developed and verified using GastroPlus™ software for both adults and children (2-12 years old, 12-52 kg). The biopharmaceutics properties and GIT physiological parameters were evaluated by sensitivity analysis. High doses were simulated assuming a worst case scenario, that is, the dose of 200 mg for adults and 5 mg/kg (up to the maximum of 200 mg) for 2-year-old children. Although several authors have suggested that ontogeny may have an effect on gastrointestinal fluid volume, our study found no evidence of interference between fluid and dose volumes with in vivo dissolution of LTG. The most impactful parameter was found to be the gastric transit time. Therefore, the hypothesis is developed to examine whether LTG exhibits characteristics of a BCS II classification in vitro while showing BCS I-like behavior in vivo. This hypothesis could act as a base for conducting novel studies on model-informed precision dosing, tailored to specific populations and clinical conditions. In addition, it could be instrumental in assessing the influence of various release profiles on in vivo performance for both adult and pediatric populations.

Long-Term Outcome of Temporal Lobe Epilepsy Surgery in 621 Patients With Hippocampal Sclerosis: Clinical and Surgical Prognostic Factors.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60-70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Hypoxemia following generalized convulsive seizures: Risk factors and effect of oxygen therapy.

OBJECTIVE: To analyze the factors that determine the occurrence or severity of postictal hypoxemia in the immediate aftermath of a generalized convulsive seizure (GCS). METHODS: We reviewed the video-EEG recordings of 1,006 patients with drug-resistant focal epilepsy included in the REPO2MSE study to identify those with ≥1 GCS and pulse oximetry (SpO2) measurement. Factors determining recovery of SpO2 ≥ 90% were investigated using Cox proportional hazards models. Association between SpO2 nadir and person- or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS: A total of 107 GCS in 73 patients were analyzed. A transient hypoxemia was observed in 92 GCS (86%). Rate of GCS with SpO2 <70% dropped from 40% to 21% when oxygen was administered early (p = 0.046). Early recovery of SpO2 ≥90% was associated with early administration of oxygen (p = 0.004), absence of postictal generalized EEG suppression (PGES) (p = 0.014), and extratemporal lobe epilepsy (p = 0.001). Lack of early administration of O2 (p = 0.003), occurrence of PGES (p = 0.018), and occurrence of ictal hypoxemia during the focal phase (p = 0.022) were associated with lower SpO2 nadir. CONCLUSION: Postictal hypoxemia was observed in the immediate aftermath of nearly all GCS but administration of oxygen had a strong preventive effect. Severity of postictal hypoxemia was greater in temporal lobe epilepsy and when hypoxemia was already observed before the onset of secondary GCS.

Qualidade de vida e eventos adversos de pacientes com epilepsia farmacorresistente em uso de lamotrigina / Quality of life and adverse events of patients with drug-resistant epilepsy using lamotrigine

Modelo do estudo: Estudo transversal. Introdução: O tratamento farmacológico é a primeira opção para o tratamento da epilepsia, e cerca de 40% dos pacientes necessitam de politerapia para melhor controle das crises epilépticas, o que pode estar associado ao aumento de eventos adversos e comprometimento da qualidade de vida. Objetivos: Avaliar a qualidade de vida de pacientes com epilepsia farmacoresistente em uso de lamotrigina (LTG), bem como verificar a associação dos eventos adversos dos antiepilépticos com a qualidade de vida. Metodologia: Este estudo transversal foi realizado com 75 pacientes com epilepsia farmacorresistente em uso LTG atendidos em um Ambulatório de Epilepsia de Difícil Controle de Ribeirão Preto-SP, no período de maio/2011 a abril/2012. As variáveis clínicas analisadas foram a qualidade de vida (Quality of Life in Epilepsy - Qolie-31) e o perfil de eventos adversos (AEP ­ Adverse Events Profile Questionnaire). Dados sociodemográficos e farmacoterapêuticos foram coletados através dos prontuários dos pacientes. Este trabalho foi aprovado pelo Comitê de Ética em Pesquisa do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), cujo número do processo é 8791/2010. Resultados: Os eventos adversos mais frequentes foram sonolência e dificuldade de concentração. Além disso, observou-se baixos escores em todos os domínios relacionados à qualidade de vida (Qolie-31). Conclusão: A qualidade de vida possui associação inversamente significativa com os eventos adversos, nos pacientes em uso de antiepilépticos (p<0,01). (AU)

Study design: Cross-sectional study. Introduction: Pharmacological treatment is the first option to treat epilepsy, and about 40% of patients require polytherapy to better control epileptic seizures, which may be associated with an increase in adverse events and impairment of quality of life. Objective: To evaluate the quality of life of patients with pharmacoresistant epilepsy using lamotrigine (LTG), as well as to verify the association of adverse events with antiepileptic drugs with quality of life. Methods: This cross-sectional study was carried out with 75 patients with drugresistant epilepsy using LTG, in a Clinic of Epilepsy of Difficult Control of Ribeirão Preto-SP, from May/2011 to April / 2012. The clinical variables analyzed were Quality of Life in Epilepsy (QOLIE31) and the Adverse Events Profile Questionnaire (AEP). Socio-demographic and pharmacotherapeutic data were collected through patient records. This study was approved by the Research Ethics Committee of the General Hospital of the Medical School of Ribeirão Preto of the University of São Paulo (HCFMRP-USP), whose case number is 8791/2010. Results: The most frequent adverse events were somnolence and difficulty concentrating. In addition, low scores were observed in all domains related to quality of life (Qolie-31). Conclusion: Quality of life has an inverse association with adverse events in patients using antiepileptic drugs (p <0.01). (AU)

Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

ABSTRACT The purpose of this work was to evaluate the influence of the clinical profile on lamotrigine (LTG) plasma concentrations from patients with refractory epileptic seizures. In this cross-sectional study, therapeutic monitoring of LTG, and questionnaires with 75 patients with refractory epileptic seizures of a Hospital in Ribeirão Preto-SP-Brazil were performed. The multiple linear regression model was used to verify association between the LTG plasma concentrations and the independent variables. Covariance analysis was used to compare the mean LTG plasma concentration among the co-medication groups. The LTG plasma concentration was associated both with the LTG dosage (mg/kg/day) (p=0.0096) and with the use of first generation antiepileptic drugs (AED) (p<0.01), being carbamazepine (CBZ) and phenytoin (PHT), the AEDs showing the most prominent influence in reducing LTG plasma concentrations. Adverse events, adherence to the pharmacological treatment, and epileptic seizures frequency, did not show significant correlation with LTG plasma concentration values. The conclusion is that LTG plasma concentration is significantly influenced by the LTG dosage and by the concomitant use of a first generation AED.

An investigation of the influence of patient-related factors and comedications on lamotrigine clearance in patients with epilepsy.

Lamotrigine (LTG) is one of the most widely used antiepileptic drugs. Confusion still exists in the literature as to the relative influence of age, body weight, and concomitant drug therapy on LTG pharmacokinetics. So, the objective of this study is to evaluate the influence of patient-related factors and comedication on LTG apparent oral clearance (CL/F). A therapeutic drug-monitoring database was used to identify steady-state plasma LTG concentrations in 210 patients. LTG CL/F values were calculated for each patient according to the equation CL/F (L/h per kg) = LTG daily dose (mg/kg)/Css (steady state concentration) (mg/L) × 24 h. A linear-regression model was used to assess the influence of gender, dose, age, and body weight in LTG CL/F. The influence of comedication on LTG CL/F was investigated by applying the Bonferroni post-test. The lowest LTG CL/F was found in patients comedicated with valproate (VPA) (mean, 0.0183 L/h per kg), followed by patients receiving VPA + enzyme inducers (0.0271 L/h per kg), patients on LTG monotherapy (0.0298 L/h per kg) and patients comedicated with enzyme inducers (0.056 L/h per kg) LTG CL/F correlated significantly with LTG dose (P < 0.01), but showed no significant relationship with gender, weight, and age. LTG CL/F is influenced by the type of antiepileptic comedication. The correlation with dose may be a spurious finding related to the fact that physicians, in adjusting dosage according to clinical response, are more likely to use larger doses in patients with high clearance values.

Adhesio interthalamica and cavum septum pellucidum in mesial temporal lobe epilepsy.

The absence of the adhesio interthalamica (AI; also called interthalamic adhesion or massa intermedia) and the presence of a large cavum septum pellucidum (CSP) later in life have been related to neurodevelopmental alterations and have not been systematically investigated in epilepsy to date. This study carried out a MRI evaluation of the AI and CSP in a large sample with mesial temporal lobe epilepsy (MTLE). A total of 179 patients, classified according to the side of the epileptogenic focus, and 156 age- and sex-balanced healthy controls were assessed. Between-group comparisons of the prevalence and length of both AI and CSP were conducted. Neuropsychological assessments were also performed in 160 MTLE patients. The patients exhibited reduction in the AI prevalence (P < 0.05; FDR-uncorrected) and length (P < 0.05; FDR-corrected) when compared to controls. Patients without AI showed lower scores in a proportion of neuropsychological tests than patients with AI. No CSP differences were found between MTLE patients and controls. These results support that AI anomalies have clinical significance in MTLE, as well as indicate that neurodevelopmental alterations may be implicated in this disorder.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

OBJECTIVE: To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). METHODS: We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS: A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). CONCLUSION: The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen.

Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. METHODS: A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. RESULTS: Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. CONCLUSIONS: This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE-HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS.

The social context and the need of information from patients with epilepsy: evaluating a tertiary referral service.

OBJECTIVE: Characterize the social profile and the need of information from patients with refractory epilepsy. METHOD: A semi-structured questionnaire was applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy and any doubts about epilepsy. RESULTS: Patients were highly dependent on having a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the population was unemployed, and 26% confirmed receiving social security benefits due to epilepsy. Twenty-nine percent of the population reached high school. Eighty-five percent of the patients had at least one doubt about epilepsy; treatment and epilepsy aspects in general were the main topics. CONCLUSION: As observed in developed countries, patients with refractory epilepsy from a developing country also have high rates of unemployment and low educational levels. The results raise a concern about the need of information about epilepsy by patients and their families, urging the necessity to invest in strategies to solve this deficiency in knowledge.

The social context and the need of information from patients with epilepsy: evaluating a tertiary referral service / O contexto social e a necessidade de informações de pacientes com epilepsia: avaliando um serviço terciário de referência

Objective Characterize the social profile and the need of information from patients with refractory epilepsy. Method A semi-structured questionnaire was applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy and any doubts about epilepsy. Results Patients were highly dependent on having a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the population was unemployed, and 26% confirmed receiving social security benefits due to epilepsy. Twenty-nine percent of the population reached high school. Eighty-five percent of the patients had at least one doubt about epilepsy; treatment and epilepsy aspects in general were the main topics. Conclusion : As observed in developed countries, patients with refractory epilepsy from a developing country also have high rates of unemployment and low educational levels. The results raise a concern about the need of information about epilepsy by patients and their families, urging the necessity to invest in strategies to solve this deficiency in knowledge. .

Objetivo : Caracterizar o perfil social e a necessidade de informações por parte de pacientes com epilepsia refratária. Método Um questionário semi-estruturado foi aplicado a 103 pacientes para investigar aspectos sociodemográficos, farmacoterapia e quaisquer dúvidas sobre epilepsia. Resultados Os pacientes mostraram-se altamente dependentes de um fornecimento gratuito e acessível de drogas antiepilépticas. Sessenta e oito por cento da população estava desempregada, e 26% confirmaram receber algum benefício social devido à epilepsia. Vinte e nove por cento da população alcançou ensino médio. Oitenta e cinco por cento dos pacientes tinha ao menos uma dúvida sobre epilepsia; tratamento e aspectos gerais da epilepsia foram os principais temas. Conclusão Tal qual observado em países desenvolvidos, pacientes com epilepsia refratária em países em desenvolvimento também apresentam altas taxas de desemprego e baixos níveis educacionais. Os resultados são preocupantes no que diz respeito à necessidade de informações sobre epilepsia por parte dos pacientes e seus familiares, apontando a necessidade de se investir em estratégias que solucionem esta deficiência de conhecimento. .

Characteristics of mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis.

Recent observations suggest that neurocysticercosis (NCC) might act as an initial precipitating injury (IPI) causing mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). A total of 191 patients from Brazil, a country in which NCC is endemic, were surgically treated for MTLE-HS, and subsequent findings for patients with MTLE-HS were compared with those of patients with MTLE-HS plus NCC. Seventy-one patients (37,2%) presented chronic findings of NCC (cNCC). MTLE-HS plus cNCC was significantly more common in women (O.R.=2.45; 95%CI=1.30-4.60; p=0.005), in patients with no history of classical forms of IPI (O.R.=2.67; 95%CI=1.37-5.18; p=0.004), and in those with bi-temporal interictal spikes on video-EEG (O.R.=2.00; 95%CI=1.07-3.73; p=0.03). Single cNCC lesions were observed to occur significantly more often on the same side as hippocampal sclerosis, a finding suggesting an anatomical relationship between NCC and MTLE-HS. Taken together, our results suggest that NCC may be a marker, or contributes to or even causes MTLE-HS. Based on our findings, we propose two distinct, non-excluding, and potentially synergistic mechanisms involved in the development of MTLE-HS in NCC, one of them being inflammatory-mediated, while the other is electrogenic-mediated. Taken together, our observations may provide further evidence suggesting a role of NCC in the genesis or development of MTLE-HS.

Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Analysis of oxcarbazepine and the 10-hydroxycarbazepine enantiomers in plasma by LC-MS/MS: application in a pharmacokinetic study.

Oxcarbazepine is a second-generation antiepileptic drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures or generalized tonic-clonic seizures in adults and children. It undergoes rapid presystemic reduction with formation of the active metabolite 10-hydroxycarbazepine (MHD), which has a chiral center at position 10, with the enantiomers (S)-(+)- and R-(-)-MHD showing similar antiepileptic effects. This study presents the development and validation of a method of sequential analysis of oxcarbazepine and MHD enantiomers in plasma using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Aliquots of 100 µL of plasma were extracted with a mixture of methyl tert-butyl ether: dichloromethane (2:1). The separation of oxcarbazepine and the MHD enantiomers was obtained on a chiral phase Chiralcel OD-H column, using a mixture of hexane:ethanol:isopropanol (80:15:5, v/v/v) as mobile phase at a flow rate of 1.3 mL/min with a split ratio of 1:5, and quantification was performed by LC-MS/MS. The limit of quantification was 12.5 ng oxcarbazepine and 31.25 ng of each MHD enantiomer/mL of plasma. The method was applied in the study of kinetic disposition of oxcarbazepine and the MHD enantiomers in the steady state after oral administration of 300 mg/12 h oxcarbazepine in a healthy volunteer. The maximum plasma concentration of oxcarbazepine was 1.2 µg/mL at 0.75 h. The kinetic disposition of MHD is enantioselective, with a higher proportion of the S-(+)-MHD enantiomer compared to R-(-)-MHD and an AUC(0-12) S-(+)/R-(-) ratio of 5.44.

Opercular myoclonic-anarthric status epilepticus due to glutamic acid decarboxylase antibody-associated encephalitis.

We report a patient who was diagnosed with opercular myoclonic-anarthric status epilepticus and found to have glutamic acid decarboxylase antibody (GADA)-associated encephalitis, a previously unrecognised aetiology of this condition. The patient was a 23-year-old female admitted for investigation of focal myoclonic status epilepticus in the right side of the face and glossopharyngeal area. Intravenous corticosteroid was administered and improvement was observed in seizure activity and overall general health. A video sequence of opercular myoclonia is included. Due to the presence of inflammatory elements based on brain MRI and CSF studies, a decision to investigate autoimmune encephalitis was undertaken. Anti-GAD65 radioimmunoassay was markedly positive. This case study highlights the need for awareness of the clinical presentation of GADA-associated encephalitis. [Published with video sequences].

Cognitive and surgical outcome in mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis: a cohort study.

BACKGROUND: Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC. METHODS: Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC. FINDINGS: cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05-2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69-1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27-3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20-5.32; p = 0.012). INTERPRETATION: cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.

Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center.

OBJECTIVE: To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. METHOD: Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. RESULTS: Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% and 58.9% of the patients, respectively). Among the new agents, lamotrigine was the most commonly prescribed (36.6% of the patients). At least one old agent was identified in 103 out of the 104 polytherapies, while at least one new agent was prescribed to 70.5% of the population. The most prevalent combination was carbamazepine + clobazam + lamotrigine. The mean AED load found was 3.3 (range 0.4-7.7). CONCLUSION: The pattern of use of individual drugs, although consistent with current treatment guidelines, is strongly influenced by the public health system.

Addressing overtreatment in patients with refractory epilepsy at a tertiary referral centre in Brazil.

BACKGROUND: Patients with refractory epilepsy often have impaired quality of life (QOL) as a consequence of seizures and adverse effects of antiepileptic drugs. We assessed the impact of adverse effects on QOL and the utility of a structured instrument to help the physician manage adverse effects in patients with refractory epilepsy. METHODS: Clinical characteristics, drug treatment and adverse effects were evaluated in 102 patients with refractory epilepsy at a single tertiary referral centre. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE-31) questionnaires were completed at baseline and after six months. At baseline, patients with a high burden of adverse effects (AEP scores ≥45) were randomized to an intervention or control group. AEP scores in the intervention group were available to the physician as an instrument to help to reduce adverse effects. RESULTS: Ninety-five patients (93.1%) were on polytherapy. Sixty-six completed the questionnaires and, of these, 43 (65.1%) had a high AE burden and were randomized to the intervention and control group. QOLIE-31 scores were inversely correlated with AEP scores at both visits. Among randomized patients, AEP scores tended to decrease between the baseline and the final visit without significant differences between groups (intervention group: 54.1 ±â€Š6.1 vs 51.1 ±â€Š9.1; control group: 55.8 ±â€Š5.8 vs 50.5 ±â€Š12.2). QOLI-31 scores did not change substantially between visits (intervention group: 45.9 ±â€Š17.4 vs 48.4 ±â€Š14; control group: 47.5 ±â€Š15.7 vs 45.2 ±â€Š18.9). CONCLUSION: A significant proportion of patients had a high toxicity burden which had an impact on their QOL. Reduction of overtreatment is a difficult challenge which cannot be addressed solely by providing a structured assessment of adverse effects, but requires a more comprehensive approach aimed at optimizing the many components of the management strategy.

Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy.

To assess whether levetiracetam elimination is influenced by enzyme inducing antiepileptic drugs (EIAEDs), serum levetiracetam levels were determined at frequent intervals after a single oral 1000mg dose in 15 subjects co-medicated with EIAEDs and 15 matched controls. The EIAED group showed a higher levetiracetam oral clearance (p=0.01) and a shorter half-life (p=0.02) than controls. Although the magnitude of interaction is relatively modest, it could have clinical significance for some patients.