Long-Term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures.

OBJECTIVE: Evaluate long-term efficacy (percent seizure frequency reduction and responder rates), safety, and tolerability of adjunctive cenobamate in an open-label extension (OLE) of the randomized, double-blind, placebo-controlled study. METHODS: Patients (aged 18-70 years) with uncontrolled focal seizures despite treatment with 1-3 antiseizure medications who completed the 18-week double-blind study (n=360) could enter the OLE, where they underwent a 2-week blinded conversion to cenobamate (target dose, 300 mg/day; min/max, 50/400 mg/day). RESULTS: Three hundred fifty-five patients were included in the OLE safety population (265 originally randomized to cenobamate, 90 originally randomized to placebo), and 354 were included in the OLE modified intent-to-treat population. As of July 2019, 58.9% (209/355) of patients were continuing cenobamate treatment and 141 had discontinued, including 16.6% (59/355) due to lack of efficacy, 8.7% (31/355) due to withdrawal by patient, and 7.6% (27/355) due to adverse events. Median (range) duration of OLE exposure was 53.9 (1.1-68.7) months. Retention rates at 12, 24, 36, and 48 months were 83%, 71%, 65%, and 62%, respectively. Median percent seizure frequency reduction over baseline increased with each 6-month OLE interval, up to 76.1% at months 43-48. Among observed patients, 16.4% (36/220) achieved 100% and 39.1% (86/220) achieved ≥90% seizure reduction during >36-48 months. Among the initial OLE mITT population, 10.2% (36/354) of patients achieved 100% and 24.3% (86/354) achieved ≥90% seizure reduction during >36-48 months. Similar to the double-blind study, adverse events (AEs) included dizziness, somnolence, fatigue, and headache. Serious AEs occurred in 20.3% (72/355) of patients. CONCLUSION: Long-term efficacy, including 100% and ≥90% seizure reduction, was sustained during 48 months of cenobamate treatment, with 71% retention at 24 months. No new safety issues were identified. These results confirm the findings of the double-blind study and support the potential long-term clinical benefit of cenobamate. REGISTRATION: ClinicalTrials.gov NCT01866111. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that oral Cenobamate 50-400 mg/day is effective as an adjunctive treatment for the long-term management of patients with uncontrolled focal seizures previously treated with 1 to 3 ASMs.

Efficacy and safety of adjunctive cenobamate: Post-hoc analysis of study C017 in patients grouped by mechanism of action of concomitant antiseizure medications.

PURPOSE: To assess how efficacy and safety outcomes were affected when cenobamate was co-administered with antiseizure medications (ASMs) that use either sodium channel blocker (SCB) or non-sodium channel blocker (non-SCB) mechanisms of action (MoAs) in patients with uncontrolled focal seizures. METHODS: An exploratory post-hoc analysis of a randomized, double-blind, placebo-controlled clinical study (YKP3089C017) was conducted. Baseline concomitant ASMs were grouped as either those that employed an SCB or non-SCB MoA. Efficacy was examined by cenobamate dose (100 mg, 200 mg, and 400 mg/day) and concomitant ASM group using responder rates (≥50%, ≥75%, ≥90% seizure reduction; 100% seizure reduction/seizure freedom) during the maintenance phase and median percentage seizure reduction during the double-blind period. Treatment-emergent adverse events (TEAEs) were examined in the double-blind period. RESULTS: When co-administered with SCBs or non-SCBs, significantly higher percentages of patients achieved ≥50%, ≥75%, and ≥90% responder rates with cenobamate 200 mg/day and/or 400 mg/day versus placebo. Additionally, significantly higher percentages of patients achieved seizure freedom with cenobamate 400 mg/day versus placebo (SCB group, 17.5% versus 1.2%; non-SCB group, 40.0% versus 0.0%). Patients receiving 200 mg/day and 400 mg/day and concomitant SCBs and all patients taking cenobamate combined with non-SCB concomitant ASMs had significantly greater median percentage reductions in focal seizure frequency versus placebo. TEAEs were similar across groups; however, dizziness was more frequently reported in the SCB group. CONCLUSION: Cenobamate is a highly effective new treatment option for patients with uncontrolled focal seizures when co-administered with SCB or non-SCB ASMs.

Initiating antiepilepsy treatment: An update of expert consensus in Spain.

Following publication in 2014 of the International League Against Epilepsy (ILAE) official report changing the definition of epilepsy, a number of questions remain unresolved in regard to deciding when to start treatment and to the choice of a particular antiseizure medication (ASM). This study uses a Delphi method to update consensus among a panel of experts on the initiation of epilepsy treatment in order to provide insight regarding those questions. The study was undertaken in four phases. Firstly, a multi-center steering committee met to review relevant bibliography and to draft a questionnaire. Secondly, a panel of neurologists specialized in epilepsy was selected and convened. Thirdly, an online survey was carried out in two rounds. Fourthly, the final results were discussed at a face-to-face meeting of the steering committee to draw conclusions. The final questionnaire focused on three independent sections: the decision to commence ASM in different clinical situations, the choice of initial monotherapy depending on the type of epilepsy and the patient's age/sex (including childbearing potential), and the choice of initial monotherapy depending on comorbidity. In these two latter sections, fourteen ASMs approved for monotherapy use by the EMA and available in Spain were considered. Regarding the decision as to when to commence treatment, the results show agreement exists to initiate treatment following a first generalized tonic-clonic seizure or a focal seizure if the electroencephalography (EEG) reveals epileptiform activity, if the MRI reveals a lesion, or when it occurs in elderly patients. With respect to the choice of initial monotherapy depending on the type of epilepsy and the patient's age/sex profile, it is agreed to avoid valproic acid (VPA) in women with childbearing potential, with levetiracetam (LEV) and lamotrigine (LTG) being the preferable options in generalized epilepsy. In focal epilepsy, the options are broader, particularly in men, and include the most recent ASMs approved for monotherapy. In the elderly, LEV, lacosamide (LCM), eslicarbazepine acetate (ESL) and LTG are considered the most suitable drugs for initiating treatment. With regard to comorbidities, the recommendation is to avoid enzyme inducing ASMs, with LEV, the most recent ASMs approved for monotherapy and LTG being the preferred options. In conclusion, as the ILAE definition states, there are different situations that lead to treatment initiation after a first seizure. When choosing the first ASM, the type of epilepsy, childbearing potential and drug-drug interaction are key factors.

Percepción de la imagen corporal y su relación con el estado nutricional y emocional en escolares de 10 a 13 años de tres escuelas en Barranquilla (Colombia) / Perception of body image and its relationship to the nutritional and emotional state in schoolchildren 10-13 years of three schools in Barranquilla (Colombia)

Resumen Objetivo: evaluar la percepción de la imagen corporal y su relación con el estado nutricional y emocional en escolares de 10 a 13 años en tres colegios públicos de Barranquilla. Materiales y métodos: estudio descriptivo transversal, en muestra de 262 escolares de tres colegios públicos. Previo consentimiento informado de padres y asentimiento de participantes, se tomaron mediciones biométricas y realizaron encuestas, empleando cuestionario de factores sociodemográficos, Test Krece Plus sobre hábitos alimentarios y de Actividad Física, Escala de Autoestima de Rosemberg, cuestionario Goldberg para ansiedad y depresión y test de las siluetas para imagen corporal. Resultados: La media de edad fue de 11.39 años (± 1.11) y el 61.5 % varones. El 22,6 % de la población presentó distorsión en su imagen corporal; el 67,8 % de los adolescentes con imagen distorsionada tuvo un Índice de Masa Corporal normal; de ellos, el 21.8 % tuvo malos hábitos alimentarios y el 17.2 % malos hábitos de actividad física; las alteraciones emocionales se presentaron en un 8.8 % baja autoestima, en un 7.3 % ansiedad y en un 6.9 % depresión. Se obtuvo tendencia en la asociación como factor determinante con el sexo masculino (p=0.008) y protector para la actividad fisca (p=0.000) y el IMC bajo (p=0.000) Conclusiones: Predominó la adecuada percepción de imagen corporal. La distorsión fue mayor en hombres, en el estado nutricional normal, los inadecuados hábitos alimentarios y de actividad física y autoestima baja. Hubo tendencia a la asociación con el sexo masculino, protector para la actividad física y el IMC bajo.

Abstract Objective: To evaluate the perception of body image and its relationship to the nutritional and emotional status in school children 10-13 years in three public schools in Barranquilla. Methods: Cross-sectional study in a sample of 262 students from three public schools. Prior informed consent of parents and assent of participants, and biometric measurements were taken surveys conducted using: a questionnaire on sociodemographic factors, test Krece Plus on eating habits and physical activity, Rosenberg Self Esteem Scale, Goldberg questionnaire for anxiety and depression and test for body image silhouettes. Results: Mean age was 11.39 years (± 1.11) and 61.5% were male. 22.6% of the population showed distorted body image; 67.8% of adolescents had a distorted image index normal weight, of which 21.8% had poor eating habits and 17.2%, poor physical activity habits; emotional disturbances occurred in 8.8% low self esteem, anxiety, 7.3% and 6.9% depression. Trend was obtained in the association as a factor in males (p = 0.008), and protection for Fisca activity (p = 0.000) and low BMI (p = 0.000) Conclusions: The prevailing perception of appropriate body image. The distortion was higher in men, in the normal nutritional status, inadequate food and physical activity habits and low self esteem. There was a trend toward association with the male protector for physical activity and low BMI.

[Combined treatment with antiepileptic drugs. Andalusian Epilepsy Guide 2015]. / Tratamiento combinado con fármacos antiepilépticos. Guía Andaluza de Epilepsia 2015.

AIMS: The aim of this study was to draw up a set of recommendations based on scientific evidence and in agreement with authors and reviewers, which address fundamental issues concerning the combination of antiepileptic drugs. DEVELOPMENT: A committee of 11 experts belonging to the Sociedad Andaluza de Epilepsia (SAdE--Andalusian Epilepsy Society), of whom seven were neurologists, three were neuropaediatricians and one was a neurologist-neurophysiologist, all of them with long experience in epilepsy, promoted a comprehensive literature review among 55 experts in epilepsy who were members of the SAdE, with the aim of searching for any evidence that might be available on diagnostic or therapeutic matters in epilepsy. The guidelines were set out in 35 chapters. One of the chapters addressed the combination of antiepileptic drugs in the treatment of epilepsy. Taking 77 bibliographical references and the consensus view of authors and reviewers as their starting point, a set of easily applicable recommendations were drawn up. CONCLUSIONS: Combining antiepileptic drugs in patients with epilepsy whose seizures are not controlled with a single drug can, on many occasions, result in their going back into remission. There are a series of factors related with the type of epilepsy and characteristics of the patient and with the antiepileptic drugs to be used in combination that may favour a successful therapeutic outcome. Over-treatment with the combination of antiepileptic drugs must be avoided as far as possible. The results of this review provide a set of recommendations regarding combined treatment with antiepileptic drugs, based on scientific evidence and the agreement of authors, that are simple, useful and easy to apply at the different levels of healthcare.

TITLE: Tratamiento combinado con farmacos antiepilepticos. Guia Andaluza de Epilepsia 2015.Objetivo. Elaborar unas recomendaciones basadas en evidencias cientificas y en consenso de los autores y revisores, que aborden las cuestiones basicas acerca de la combinacion de farmacos antiepilepticos. Desarrollo. Un comite de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia (SAdE), constituido por siete neurologos, tres neuropediatras y un neurologo-neurofisiologo, todos con especial competencia en epilepsia, promovieron la realizacion de una revision bibliografica exhaustiva entre 55 expertos en epilepsia pertenecientes a la SAdE, en busca de evidencias disponibles relacionadas con temas diagnosticos o terapeuticos en epilepsia. La guia se estructuro en 35 capitulos. Uno de los capitulos abordo la combinacion de farmacos antiepilepticos en el tratamiento de la epilepsia. Basandose en 77 citas bibliograficas y en la opinion consensuada de autores y revisores, se confecciono una serie de recomendaciones de facil aplicacion. Conclusiones. La combinacion de farmacos antiepilepticos en los pacientes con epilepsia cuyas crisis no estan controladas con un solo farmaco puede conseguir en numerosas ocasiones que entren en remision. Existe una serie de factores relacionados con el tipo de epilepsia y caracteristicas del paciente y con los farmacos antiepilepticos que se van a utilizar en combinacion que pueden favorecer el exito terapeutico. Se debe evitar en lo posible el sobretratamiento con la combinacion de farmacos antiepilepticos. Los resultados de esta revision proveen unas recomendaciones sobre el tratamiento combinado con farmacos antiepilepticos, basadas en evidencias cientificas y en el consenso de los autores, utiles, sencillas y aplicables en los diferentes niveles asistenciales.

Tratamiento combinado con fármacos antiepilépticos. Guía Andaluza de Epilepsia 2015 / Combined treatment with antiepileptic drugs. Andalusian Epilepsy Guide 2015

Objetivo. Elaborar unas recomendaciones basadas en evidencias científicas y en consenso de los autores y revisores, que aborden las cuestiones básicas acerca de la combinación de fármacos antiepilépticos. Desarrollo. Un comité de 11 expertos pertenecientes a la Sociedad Andaluza de Epilepsia (SAdE), constituido por siete neurólogos, tres neuropediatras y un neurólogo-neurofisiólogo, todos con especial competencia en epilepsia, promovieron la realización de una revisión bibliográfica exhaustiva entre 55 expertos en epilepsia pertenecientes a la SAdE, en busca de evidencias disponibles relacionadas con temas diagnósticos o terapéuticos en epilepsia. La guía se estructuró en 35 capítulos. Uno de los capítulos abordó la combinación de fármacos antiepilépticos en el tratamiento de la epilepsia. Basándose en 77 citas bibliográficas y en la opinión consensuada de autores y revisores, se confeccionó una serie de recomendaciones de fácil aplicación. Conclusiones. La combinación de fármacos antiepilépticos en los pacientes con epilepsia cuyas crisis no están controladas con un solo fármaco puede conseguir en numerosas ocasiones que entren en remisión. Existe una serie de factores relacionados con el tipo de epilepsia y características del paciente y con los fármacos antiepilépticos que se van a utilizar en combinación que pueden favorecer el éxito terapéutico. Se debe evitar en lo posible el sobretratamiento con la combinación de fármacos antiepilépticos. Los resultados de esta revisión proveen unas recomendaciones sobre el tratamiento combinado con fármacos antiepilépticos, basadas en evidencias científicas y en el consenso de los autores, útiles, sencillas y aplicables en los diferentes niveles asistenciales (AU)

Aim. To draw up a set of recommendations based on scientific evidence and in agreement with authors and reviewers, which address fundamental issues concerning the combination of antiepileptic drugs. Development. A committee of 11 experts belonging to the Sociedad Andaluza de Epilepsia (SAdE - Andalusian Epilepsy Society), of whom seven were neurologists, three were neuropaediatricians and one was a neurologist-neurophysiologist, all of them with long experience in epilepsy, promoted a comprehensive literature review among 55 experts in epilepsy who were members of the SAdE, with the aim of searching for any evidence that might be available on diagnostic or therapeutic matters in epilepsy. The guidelines were set out in 35 chapters. One of the chapters addressed the combination f antiepileptic drugs in the treatment of epilepsy. Taking 77 bibliographical references and the consensus view of authors and reviewers as their starting point, a set of easily applicable recommendations were drawn up. Conclusions. Combining antiepileptic drugs in patients with epilepsy whose seizures are not controlled with a single drug can, on many occasions, result in their going back into remission. There are a series of factors related with the type of epilepsy and characteristics of the patient and with the antiepileptic drugs to be used in combination that may favour a successful therapeutic outcome. Over-treatment with the combination of antiepileptic drugs must be avoided as far as possible. The results of this review provide a set of recommendations regarding combined treatment with antiepileptic drugs, based on scientific evidence and the agreement of authors, that are simple, useful and easy to apply at the different levels of healthcare (AU)

Adult Prevalence of Epilepsy in Spain: EPIBERIA, a Population-Based Study.

BACKGROUND: This study assesses the lifetime and active prevalence of epilepsy in Spain in people older than 18 years. METHODS: EPIBERIA is a population-based epidemiological study of epilepsy prevalence using data from three representative Spanish regions (health districts in Zaragoza, Almería, and Seville) between 2012 and 2013. The study consisted of two phases: screening and confirmation. Participants completed a previously validated questionnaire (EPIBERIA questionnaire) over the telephone. RESULTS: A total of 1741 valid questionnaires were obtained, including 261 (14.99%) raising a suspicion of epilepsy. Of these suspected cases, 216 (82.75%) agreed to participate in phase 2. Of the phase 2 participants, 22 met the International League Against Epilepsy's diagnostic criteria for epilepsy. The estimated lifetime prevalence, adjusted by age and sex per 1,000 people, was 14.87 (95% CI: 9.8-21.9). Active prevalence was 5.79 (95% CI: 2.8-10.6). No significant age, sex, or regional differences in prevalence were detected. CONCLUSIONS: EPIBERIA provides the most accurate estimate of epilepsy prevalence in the Mediterranean region based on its original methodology and its adherence to ILAE recommendations. We highlight that the lifetime prevalence and inactive epilepsy prevalence figures observed here were compared to other epidemiological studies.

Analysis of factors influencing telephone call response rate in an epidemiological study.

Descriptive epidemiology research involves collecting data from large numbers of subjects. Obtaining these data requires approaches designed to achieve maximum participation or response rates among respondents possessing the desired information. We analyze participation and response rates in a population-based epidemiological study though a telephone survey and identify factors implicated in consenting to participate. Rates found exceeded those reported in the literature and they were higher for afternoon calls than for morning calls. Women and subjects older than 40 years were the most likely to answer the telephone. The study identified geographical differences, with higher RRs in districts in southern Spain that are not considered urbanized. This information may be helpful for designing more efficient community epidemiology projects.

Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide.

Lacosamide is approved as adjunctive therapy for focal epilepsies. The number of antiepileptic drugs (AEDs) tried is associated with prognosis. This multicenter, retrospective, observational study (LACO-EXP) in Spain in 500 adult patients with focal epilepsies examined the efficacy and tolerability of add-on lacosamide. Factors associated with better efficacy/tolerability were analyzed. After 12months, the responder rate (≥50% reduction in seizure frequency) was 57.1%, and the seizure-free rate was 14.9%. Efficacy was better when lacosamide was the first or second add-on AED, although there was a small chance to be seizure-free even for patients who had received ≤10 prior AEDs. The mechanism of action of concomitant AEDs is important in all the stages, but differences are smaller in the early stages. Lacosamide was generally well tolerated. A slower dosage-titration schedule was associated with a lower adverse event rate. Further investigation of the timing of initiation of lacosamide add-on therapy and ideal combinations of AEDs is required.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.

Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía / Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations

Con la finalidad de proponer una serie de recomendaciones del tratamiento médico antiepiléptico, en el perioperatorio de los tumores cerebrales supratentoriales, se realiza una revisión de la literatura enfocada sobre todo a la profilaxis primaria de las crisis epilépticas precoces acaecidas en el postoperatorio inmediato. Se concluye que es recomendable pautar profilaxis primaria antiepiléptica poscirugía durante una semana en los pacientes con tumor cerebral supratentorial que no han presentado crisis epilépticas. Si las crisis aparecen durante la evolución de la enfermedad, es necesario pautar un tratamiento a largo plazo. Dadas las características de estos pacientes, se recomienda usar un fármaco antiepiléptico con presentación por vía intravenosa y un perfil bajo de interacciones. El levetiracetam, seguido del valproato, parecen ser los más adecuados. Dichas recomendaciones deben considerarse como una guía general de manejo, pudiendo ser modificadas, incluso de manera significativa, por las circunstancias propias de cada caso clínico (AU)

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It's recommended a one week treatment with antiepileptic drugs in patients who didn't have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient (AU)

Validation of the Spanish version of the Side Effect and Life Satisfaction Inventory in patients with epilepsy.

OBJECTIVE: The goal of the study described here was to obtain psychometric validation of the Spanish version of the 38-item Side Effects and Life Satisfaction (SEALS) Inventory. METHODS: A cross-cultural adaptation of the inventory was performed. A total of 595 patients with epilepsy were included in a multicenter cross-sectional study. The SEALS Inventory was completed, together with the Hospital Anxiety and Depression Scale and SF-12 Health Survey. RESULTS: The mean SEALS score was 60.7. SEALS presented high internal consistency, with a Cronbach alpha coefficient of 0.93, and good test-retest reliability, with an intraclass correlation coefficient of 0.92. The pattern of correlations with the Hospital Anxiety and Depression Scale and SF-12 Health Survey indicated good convergent and divergent validity. SEALS scores discriminated patients according to epilepsy-related factors, emotional disturbances, and the generic quality of life. CONCLUSION: The Spanish version of the SEALS Inventory is a valid psychometric instrument. It may be used in routine clinical practice and in clinical trials in patients with epilepsy to capture the cognitive and behavioral aspects of quality of life.

The relationship between sleep and epilepsy.

INTRODUCTION: The relationship between epilepsy and sleep has been known since ancient times, but it is still not very well understood because of the multiple aspects involved in its analysis, as well as its reciprocal and intrinsic influences. Currently, growing acknowledgement is given to the importance of epileptic manifestations during sleep, the relationship between sleep and the quality of life in patients with epilepsy and the relevance of primary sleep pathologies on seizure control. RESULTS: The modulating effects of sleep on epileptic activity in focal and generalized epilepsies are reviewed and summarized, as well as the effects of the different sleep stages and their value in lateralization and focalization of partial epilepsies, the effects of epileptic activity on sleep structure, the consequences of sleep deprivation, the effects of antiepileptic drugs on sleep, as well the effects of primary sleep disorders on epileptic activity and sleep quality in patients with epilepsy. CONCLUSIONS: To have further knowledge of the existing relationship between epilepsy and sleep can not only aid a more expeditious diagnosis of epilepsy, but better characterize it in the context of specific diagnoses. By considering associated sleep disorders, such as the sleep apnea syndrome or insomnia, the physician can prescribe antiepileptic drugs to optimize sleep patterns, which may result not only in the better control of seizures, but also in a better quality of life for patients.

Clinical implications of mechanisms of resistance to antiepileptic drugs.

BACKGROUND: Despite the currently available armamentarium of antiepileptic drugs, seizures are not adequately controlled in about one-third of epileptic patients. The mechanisms of antiepileptic drug resistance are multiple and not fully clarified. METHODS: We conducted a literature search in PubMed and the Cochrane Library databases with the terms: "Drug Resistance" [MeSH] and "Epilepsy" [MeSH], LIMITS: added to PubMed in the last 5 years, only items with abstracts, English, Spanish, Humans. REVIEW SUMMARY: It is currently known that membrane transporter proteins are increased in brain tissue of refractory epileptic patients and in animal models of epilepsy and that overexpression of these transporters and their inhibition are correlated with a reduction and an increase, respectively, of epileptic drugs in epileptic tissue (pharmacokinetic hypothesis). It has also been shown that alterations in voltage-gated sodium channels and GABAA receptors are responsible for resistance to some epileptic drugs. These changes may be constitutional (genetically determined) or acquired (as a consequence of the seizures themselves or disease progression) and may seem alone or combined with each other (pharmacodynamic hypothesis). Associations have been shown between certain genetic polymorphisms and resistance to epileptic drugs, and although they have not been replicated by all authors, they constitute a very attractive line of research. More detailed knowledge of these molecular mechanisms will probably lead to the development of new strategies for pharmacological treatment of epilepsy.

Unilateral pallidal stimulation for segmental cervical and truncal dystonia: which side?

We present a 24-year-old man with idiopathic segmental cervical and truncal dystonia of juvenile onset. His condition improved after unilateral stimulation of the internal globus pallidus ipsilateral to the contracting sternocleidomastoid muscle.