Lacosamide monotherapy in clinical practice: A retrospective chart review.

OBJECTIVE: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. MATERIALS AND METHODS: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). RESULTS: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). CONCLUSIONS: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizures.

EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

Combination of corpus callosotomy and vagus nerve stimulation in the treatment of refractory epilepsy.

BACKGROUND: Palliative techniques such as partial corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate control of seizures in pharmacoresistant patients who are not candidates for resective surgery. OBJECTIVE: The objective of this study was to analyze the efficacy of the combination of these two techniques in patients where the first surgery had not achieved adequate control. MATERIALS AND METHODS: This is a retrospective review of 6 patients with refractory epilepsy in which both types of surgery were performed, CC and VNS. We analyzed variables such as age, sex, age at onset of epilepsy, seizure types, electroencephalogram and magnetic resonance imaging results, and number of pre- and postoperative seizures. RESULTS: Three patients first underwent VNS and then CC, and 3 patients were treated in reverse order. All patients had some improvement after the first surgery, but they continued to experience persistent falls, so a second palliative technique was used. The mean improvement after both surgeries was 89% (90% in patients first receiving CC and 87% in patients who first underwent VNS). CONCLUSIONS: In adequately studied patients who are not optimal candidates for resective surgery, palliative surgery is a choice. The combination of VNS and CC shows good results in our series, although the right order to perform both procedures has not been defined. These results should be confirmed in a larger group of patients.

Epilepsy training needs for Spanish neurologists: ARPE study results.

INTRODUCTION: This study was designed to create an updated training program on epilepsy to solve whatever problems that general neurologists may detect in patients during consults. OBJECTIVES: To understand general neurologists' training needs in order to plan a specific program that may improve/standardize the clinical management of patients with epilepsy. MATERIAL AND METHODS: 122 general neurologists non-subspecialized on epilepsy were surveyed in all regions of Spain regarding the following issues: initial diagnosis, treatment, special situations by population group and/or comorbidity, prognosis and follow-up as well as whatever other topics the training program should cover. RESULTS: Neurologists agreed that treatment was the most interesting topic for them (100%), followed by diagnosis (46.67%), special situations by population group and/or comorbidity (30%), and prognosis/follow-up (7.14%). There were insignificant differences attributable to age and sex. CONCLUSIONS: Training ensures success, provided that it takes into account pedagogical considerations and professional targets to be trained, as well as technological and formal issues.

Quality of life and economic impact of refractory epilepsy in Spain: the ESPERA study.

INTRODUCTION: Despite use of currently available anti-epileptic drugs (AED), 30% of epilepsy patients are not seizure-free. The purpose of this study was to estimate the quality of life and economic impact in Spain of drug-resistant epilepsy (DRE), as defined by the International League Against Epilepsy (ILAE). METHODS: Observational retrospective 12-month study conducted in Spain including adults with focal epilepsy treated with at least two AEDs. Direct costs (€ 2010) were calculated based on health care resources used and their official unit costs. Costs were analysed from the perspectives of the Spanish National Health System (SNS) and society. The impact of DRE on patients' quality of life was examined using the QOLIE 31-P, EQ-5D-3L, and NDDIE questionnaires. RESULTS: We analysed 263 patients out of the 304 recruited. According to ILAE criteria, 70.0% of the patients had drug-resistant epilepsy, while 20.3% achieved seizure freedom. From the viewpoint of the SNS, annual costs for resistant and seizure-free patients were € 4964 and € 2978 respectively (P<.01). Compared to resistant patients, seizure-free patients showed better scores on QOLIE-31P (70.8 vs 56.4, P<.0001) and EQ-5D-3L (75.6 vs 64.7, P<.001). Seizure-free patients showed a lower incidence of major depression compared to resistant patients according to the NDDIE scale (23 vs 8.3%, P<.05). CONCLUSIONS: Results suggest that DRE is associated with increased use of healthcare resources and consequently with higher costs, poorer quality of life and higher incidence of major depression compared to seizure-free patients, thus representing a considerable burden to the SNS and society.

River widening in mountain and foothill areas during floods: Insights from a meta-analysis of 51 European Rivers.

River widening, defined as a lateral expansion of the channel, is a critical process that maintains fluvial ecosystems and is part of the regular functioning of rivers. However, in areas with high population density, channel widening can cause damage during floods. Therefore, for effective flood risk management it is essential to identify river reaches where abrupt channel widening may occur. Despite numerous efforts to predict channel widening, most studies have been limited to single rivers and single flood events, which may not be representative of other conditions. Moreover, a multi-catchment scale approach that covers various settings and flood magnitudes has been lacking. In this study, we fill this gap by compiling a large database comprising 1564 river reaches in several mountain regions in Europe affected by floods of varying magnitudes in the last six decades. By applying a meta-analysis, we aimed to identify the types of floods responsible for more extensive widening, the river reach types where intense widening is more likely to occur, and the hydraulic and morphological variables that explain widening and can aid in predicting widening. Our analysis revealed seven groups of reaches with significantly different responses to floods regarding width ratios (i.e., the ratio between channel width after and before a flood). Among these groups, the river reaches located in the Mediterranean region and affected by extreme floods triggered by short and intense precipitation events showed significantly larger widening than other river reaches in other regions. Additionally, the meta-analysis confirmed valley confinement as a critical morphological variable that controls channel widening but showed that it is not the only controlling factor. We proposed new statistical models to identify river reaches prone to widening, estimate potential channel width after a flood, and compute upper bound width ratios. These findings can inform flood hazard evaluations and the design of mitigation measures.

Prevalence and immunological spectrum of temporal lobe epilepsy with glutamic acid decarboxylase antibodies.

BACKGROUND AND PURPOSE: High levels of glutamic acid decarboxylase (GAD)-ab were initially described in patients with stiff person syndrome, and have since also been observed in patients with other neurological diseases. Temporal lobe epilepsy (TLE) seems to be specially associated. Our purpose is to describe the prevalence of GAD-ab in patients with TLE, and to characterize the clinical-immunological profile of TLE patients with high levels of GAD-ab. METHODS: An immunological profile including GAD-ab and antinuclear, anti-DNA, anti-cardiolipin, anti-transglutaminase and antithyroid antibodies was determined in a consecutive series of patients with TLE. As adulthood onset is the least common onset in TLE + hipocampal sclerosis and febrile seizures, we selected patients whose onset was after 30 years of age, to expand the spectrum of aetiologies. Patients were divided into two groups: known aetiology, 19 patients (45%) and unknown aetiology, 23 (55%). The clinical-immunological study included TLE patients with high GAD-ab levels (>1000 IU). RESULTS: Amongst 42 patients, serum GAD-ab levels were positive in 5 (152-11, 963 IU/ml), all from the unknown aetiology group. Thus, GAD-ab levels were positive in 21.7% and high in 8.7% of the unknown aetiology group. The immunological profile study included nine patients (seven pharmacoresistant), of whom six were women (66%) with mean age 41 years. Three patients reported acute debut, four (44%) insulin-dependent diabetes mellitus, five (55%) other concomitant autoimmune diseases, four (44%) memory impairment and four moderate-to-severe mood disturbance. Intrathecal synthesis of GAD-ab was observed in seven patients (77%). CONCLUSIONS: Temporal lobe epilepsy with GAD-ab is not a rare condition. In the subgroup of patients with high titres, this epilepsy is often pharmacoresistant and associated with memory impairment, depression and other autoimmune diseases.

Impact of a multidimensional infection control strategy on central line-associated bloodstream infection rates in pediatric intensive care units of five developing countries: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control strategy including a practice bundle to reduce the rates of central line-associated bloodstream infection (CLAB) in patients hospitalized in pediatric intensive care units (PICUs) of hospitals, which are members of the INICC, from nine cities of five developing countries: Colombia, India, Mexico, Philippines, and Turkey. METHODS: CLAB rates were determined by means of a prospective surveillance study conducted on 1,986 patients hospitalized in nine PICUs, over a period of 12,774 bed-days. The study was divided into two phases. During Phase 1 (baseline period), active surveillance was performed without the implementation of the multi-faceted approach. CLAB rates obtained in Phase 1 were compared with CLAB rates obtained in Phase 2 (intervention period), after implementation of the INICC multidimensional infection control program. RESULTS: During Phase 1, 1,029 central line (CL) days were recorded, and during Phase 2, after implementing the CL care bundle and interventions, we recorded 3,861 CL days. The CLAB rate was 10.7 per 1,000 CL days in Phase 1, and in Phase 2, the CLAB rate decreased to 5.2 per 1,000 CL days (relative risk [RR] 0.48, 95% confidence interval [CI] 0.29-0.94, P = 0.02), showing a reduction of 52% in the CLAB rate. CONCLUSIONS: This study shows that the implementation of a multidimensional infection control strategy was associated with a significant reduction in the CLAB rates in the PICUs of developing countries.

Academic and employment insertion as a factor related to quality of life in patients with drug-resistant temporal lobe epilepsy. / La inserción académica y laboral como un factor asociado a la calidad de vida en pacientes con epilepsia farmacorresistente del lóbulo temporal.

INTRODUCTION: Academic and employment insertion is one of the issues that most concern people with epilepsy, but little is known about its relationship with quality of life. AIM: We aimed to analyze the effects of the academic and employment insertion on quality of life, anxiety, depression, social support, and executive functions, and the relationships among these variables in patients with drug-resistant epilepsy. PATIENTS AND METHODS: Fifty-nine patients with drug-resistant temporal lobe epilepsy were classified into two groups: with academic or employment insertion (n = 25) and without insertion (n = 34) and underwent a neuropsychological evaluation. RESULTS: Patients with insertion had a significantly better quality of life, lower trait anxiety, and higher social support, and tended to have a lower percentage of errors and higher percent conceptual level responses than those without insertion. Academic/employment insertion had indirect effects on quality of life through its relationship with global social support and trait anxiety. CONCLUSIONS: Our findings provide a model for understanding the quality of life in patients with temporal lobe epilepsy for an integral perspective of the patient and points out the key role of increased social support and reduced anxiety associated with academic and employment insertion to improve quality of life. These results could favor the implementation of programs that promote academic or employment reinsertion, considering the relevance of socio-emotional domains.

TITLE: La inserción académica y laboral como un factor asociado a la calidad de vida en pacientes con epilepsia farmacorresistente del lóbulo temporal.Introducción. La inserción académica y laboral es uno de los problemas que más preocupan a las personas con epilepsia, pero permanece sin esclarecer su relación con la calidad de vida. Objetivo. Analizar los efectos de la inserción académica y laboral en la calidad de vida, la ansiedad, la depresión, el apoyo social y las funciones ejecutivas, así como la relación entre estas variables en pacientes con epilepsia farmacorresistente. Pacientes y métodos. Cincuenta y nueve pacientes con epilepsia farmacorresistente del lóbulo temporal fueron clasificados en dos grupos, con inserción académica o laboral (n = 25) y sin inserción (n = 34), y se les realizó una evaluación neuropsicológica. Resultados. Los pacientes con inserción presentaron una calidad de vida significativamente mayor, menor ansiedad rasgo y mayor apoyo social percibido, así como una tendencia a tener un menor porcentaje de errores y un mayor porcentaje de respuestas conceptuales que los pacientes sin inserción laboral. La inserción académica/laboral tuvo efectos indirectos en la calidad de vida a través de su relación con el apoyo social y la ansiedad rasgo. Conclusiones. Nuestros hallazgos ofrecen un modelo para entender la calidad de vida en los pacientes con epilepsia del lóbulo temporal desde una perspectiva integral del paciente y señalan el papel clave del aumento del apoyo social y de la reducción de la ansiedad asociados con la inserción académica y laboral para mejorar la calidad de vida. Estos resultados podrían favorecer la implementación de programas que promuevan la reinserción académica o laboral, considerando la relevancia de variables socioemocionales.

Socio-occupational and employment profile of patients with epilepsy.

OBJECTIVE: Epilepsy has a significant impact on quality of life. Many studies have observed higher unemployment rates among patients with epilepsy. However, unemployment rates vary according to the clinical conditions, country, and group studied. METHODS: Between October 2007 and February 2008, we performed a cross-sectional multicenter epidemiological study to evaluate the socio-occupational and employment profiles of 872 adult patients with epilepsy followed in outpatient epilepsy clinics in Spain. RESULTS: Fifty-eight percent of the patients were employed at the time of the survey, 10.9% of the patients were unemployed, and 12.5% were occupationally incapacitated. CONCLUSION: Patients with epilepsy had employment rates similar to those of the general population, and slightly higher levels of unemployment. The main factors associated with unemployment and incapacity were the presence of refractory epilepsy, the occurrence of a seizure in the last 12 months, level of education, and polytherapy.

Usefulness of Video-EEG monitoring in patients with drug-resistant epilepsy.

OBJECTIVE: To evaluate the characteristics of patients on whom long-term Video-EEG monitoring is performed in a specialist centre and to assess its suitability to study refractory epilepsy patients. METHODS: A prospective analysis and study of Video-EEG monitoring was performed in a series of 100 refractory epilepsy patients from a single centre. The analysis included demographic data, the time until the first seizure, the methods used to provoke seizures, and the outcome (usefulness, change in the management, pharmacological and surgical improvement). A subgroup analysis based on diagnosis was performed. RESULTS: The study was performed mainly on young people (mean 34.4 years) and the first seizure appeared in a mean of 30hours, requiring most of the patients to withdraw the medication. Nevertheless, there were no cases of status epilepticus. The usefulness of the test was high in all the groups. The management was changed in 65% of the patients with pharmacological and surgical improvement. CONCLUSION: Long-term Video-EEG monitoring is a suitable test to study refractory epilepsy patients. The main problem in our country is accesibility.

Impact of COVID-19 on Spanish patients with Dravet syndrome and their caregivers: consequences of lockdown. / Impacto de la COVID-19 en pacientes españoles con síndrome de Dravet y sus cuidadores: consecuencias del confinamiento.

INTRODUCTION: The COVID-19 pandemic caused a state of alarm in Spain in March 2020. The necessary approach to the care of patients with Dravet syndrome (DS) makes them and their caregivers a vulnerable group in emergency situations. OBJECTIVES: To explore the impact of the COVID-19 pandemic on the management and condition of Spanish patients with DS and their caregivers and families. MATERIALS AND METHODS: Analysis of data belonging to Spanish families taken from a European online survey (14 April-17 May 2020). It included data on DS patients, on the disease and on caregivers before and after lockdown during the state of alarm. RESULTS: Sixty-nine Spanish families participated; average age of patients: 12.6 years. Except in 19% of the cases that were isolated, protective/isolation measures for patients were followed without increasing. Epilepsy remained stable, with no medication or resource/personnel availability issues. Sleep-wake pattern (61%) and behavior (41%) of patients changed. Behavior change was associated with seizures during lockdown and with caregiver emotional state (changes in 76%). Psychological support was offered to only 9% of caregivers. Thirty-eight per cent of patients did not receive remote care. CONCLUSIONS: The experience gathered during the lockdown has allowed the detection of points of improvement to ensure the proper management of DS and to keep the situation of patients and caregivers stable. All of this with a prominent role of telemedicine.

TITLE: Impacto de la COVID-19 en pacientes españoles con síndrome de Dravet y sus cuidadores: consecuencias del confinamiento.Introducción. La pandemia por COVID-19 implicó el estado de alarma en España en marzo de 2020. El abordaje necesario para el cuidado de los pacientes con síndrome de Dravet (SD) los convierte, junto con sus cuidadores, en un grupo vulnerable en situaciones de emergencia. Objetivos. Explorar el impacto de la pandemia por COVID-19 en el manejo y la condición de los pacientes españoles con SD, y de sus cuidadores y familias. Materiales y métodos. Análisis de los datos pertenecientes a familias españolas extraídos de una encuesta en línea europea (14 de abril-17 de mayo de 2020). Incluía datos de los pacientes con SD, de la enfermedad y de los cuidadores antes y después del confinamiento, durante el estado de alarma. Resultados. Participaron 69 familias españolas; edad media de los pacientes: 12,6 años. Excepto en el 19% de los casos que fueron aislados, las medidas de protección/aislamiento del paciente continuaron sin incrementar. La epilepsia se mantuvo estable, sin problemas de medicación ni disponibilidad de recursos/personal. Cambió el patrón de sueño/vigilia (61%) y la conducta (41%) de los pacientes. El cambio de conducta se asoció con las crisis durante el confinamiento y el estado anímico del cuidador (cambios en el 76%). Sólo se ofreció apoyo psicológico al 9% de los cuidadores. El 38% de los pacientes no recibió atención telemática. Conclusiones. La experiencia recogida durante el confinamiento ha permitido detectar puntos de mejora para asegurar el apropiado manejo del SD y mantener estable la situación de los pacientes y cuidadores, todo ello con un papel destacado de la telemedicina.

[Cognitive reserve as a modulating factor in the impact of surgery on visual memory and naming in temporal lobe epilepsy patients]. / La reserva cognitiva como factor modulador del impacto de la cirugía sobre la memoria visual y la denominación en pacientes con epilepsia del lóbulo temporal.

INTRODUCTION: Temporal lobe epilepsy (TLE) surgery is an effective procedure that produces cognitive changes. Factors modulating such changes have been proposed, but the influence of cognitive reserve remains unclear. OBJECTIVE: To examine the effect of intellectual quotient (IQ) on postsurgical changes in verbal fluency, naming, and verbal and visual memory in a sample of patients with TLE. PATIENTS AND METHODS: 64 adult patients with drug-resistant TLE (mean age ± SD: 39.16 ± 11.67) underwent a neuropsychological evaluation before and one year after surgery. RESULTS: Patients with high IQ showed better immediate visual memory before surgery than those with medium IQ, as well as an absence of postsurgical changes. Patients with high manipulative IQ had better naming before surgery than those with medium manipulative IQ, as well as a significant postsurgical worsening. Both before and after surgery, patients with high IQ showed better phonemic and semantic verbal fluency and short- and long-term verbal memory than those with medium IQ. CONCLUSIONS: IQ is a relevant factor in the evolution of immediate visual memory and naming after surgery in patients with TLE. Surgery does not impact on the advantage of high IQ patients in verbal fluency and verbal memory, suggesting that cognitive reserve has a positive effect on cognitive function, even after TLE surgery.

TITLE: La reserva cognitiva como factor modulador del impacto de la cirugía sobre la memoria visual y la denominación en pacientes con epilepsia del lóbulo temporal.Introducción. La cirugía de la epilepsia del lóbulo temporal (ELT) es un procedimiento eficaz que produce cambios cognitivos. Se han propuesto factores moduladores de dichos cambios, pero permanece sin esclarecer la influencia de la reserva cognitiva. Objetivo. Examinar el efecto del cociente intelectual (CI) sobre los cambios posquirúrgicos en medidas de fluencia verbal, denominación y memoria verbal y visual en una muestra de pacientes con ELT. Pacientes y métodos. Sesenta y cuatro pacientes adultos con ELT farmacorresistente (edad media ± desviación típica: 39,16 ± 11,67) fueron sometidos a una evaluación neuropsicológica antes y un año después de la cirugía. Resultados. Los pacientes con un CI alto presentaron un mejor funcionamiento de la memoria visual inmediata antes de la cirugía que los que tenían un CI medio, así como ausencia de cambios posquirúrgicos. Los pacientes con un CI manipulativo alto presentaron mejor denominación antes de la cirugía que los que tenían un CI manipulativo medio, así como un empeoramiento posquirúrgico significativo. Tanto antes como después de la cirugía, los pacientes con un CI alto presentaron mejor fluencia verbal fonémica y semántica y memoria verbal a corto y largo plazo que los que tenían un CI medio. Conclusiones. El CI es un factor relevante en la evolución de la memoria visual inmediata y de la denominación tras la cirugía en pacientes con ELT. La cirugía no repercute en la ventaja que tienen los pacientes con un CI alto en fluencia verbal y memoria verbal, lo que sugiere que la reserva cognitiva tiene un efecto positivo sobre la función cognitiva, incluso tras la cirugía de la ELT.

New therapeutic approach in Dravet syndrome and Lennox-Gastaut syndrome with cannabidiol. / Cannabidiol en los síndromes de Dravet y Lennox-Gastaut: un nuevo abordaje terapéutico.

INTRODUCTION: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are two serious epileptic syndromes with paediatric onset which are refractory to therapy and are associated with an important increase in mortality rates and comorbidities compared to the general population. These pathologies have a strong impact on the lives of patients and their families, because they undergo multiple pharmacological therapies (many of them without specific indication), with frequent changes due to poor efficacy and associated adverse effects. The specialists who care for these patients highlight unmet needs and the lack of specific, safe and effective treatments for better management of the syndrome. DEVELOPMENT: A group of four neurologists specializing in epilepsy has met to review the scientific literature and evaluate the efficacy and safety of oral solution cannabidiol in the treatment of these syndromes, both in randomized clinical trials (CT) and in some observational studies. CONCLUSIONS: Cannabidiol is positioned as an innovative therapy that allows better control of epileptic seizures and comorbidities of DS and LGS, furthermore its efficacy and safety have been evaluated in more than 700 patients. In CTs, cannabidiol significantly reduced the percentage of convulsive seizures and drop seizures compared to placebo in patients with DS and LGS respectively, which could improve their quality of life and that of their family members. The most frequent adverse effects reported were somnolence and decreased appetite. Elevated liver aminotransferase levels were also reported, especially in patients given concomitant sodium valproate. This therapy may allow better control of the epileptic seizures associated with these syndromes.

TITLE: Cannabidiol en los síndromes de Dravet y Lennox-Gastaut: un nuevo abordaje terapéutico.Introducción. Los síndromes de Dravet (SD) y Lennox-Gastaut (SLG) son dos síndromes epilépticos graves y de inicio en la edad pediátrica, refractarios al tratamiento, asociados a un notable incremento en las tasas de mortalidad y comorbilidades respecto a la población general. Suponen un fuerte impacto en la vida de los pacientes y sus familiares, ya que los pacientes están sometidos a múltiples terapias farmacológicas (muchas sin indicación específica), con cambios frecuentes debido a la escasa eficacia y a los efectos adversos. Los especialistas que les atienden destacan las necesidades no cubiertas y la falta de tratamientos específicos, seguros y eficaces para un mejor manejo de la enfermedad. Desarrollo. Se ha reunido un grupo formado por cuatro neurólogos especialistas en epilepsia para hacer una revisión de la literatura científica y evaluar los resultados de eficacia y seguridad de la solución oral de cannabidiol en el tratamiento de estos síndromes, tanto en ensayos clínicos aleatorizados como en diversos estudios observacionales. Conclusiones. El cannabidiol se sitúa como una terapia innovadora que permite un mejor control de las crisis epilépticas y comorbilidades del SD y el SLG; además, su eficacia y seguridad han sido evaluadas en más de 700 pacientes. En los ensayos clínicos redujo significativamente el porcentaje de crisis convulsivas y de caída en comparación con placebo en los pacientes con SD y SLG, respectivamente, y puede mejorar su calidad de vida y la de sus familiares. Los efectos adversos más frecuentes fueron la somnolencia y la disminución del apetito. También se notificaron niveles elevados de aminotransferasas hepáticas, especialmente en pacientes tratados concomitantemente con ácido valproico. Esta terapia podría permitir un mejor control de las crisis epilépticas asociadas a estas patologías.

Treatment initiation in epilepsy: an expert consensus in Spain.

OBJECTIVE: The goals of this study were to explore the diverse criteria surrounding indications for antiepileptic therapy and to establish a consensus on drug selection for initial monotherapy in adult patients with epilepsy. METHODS: The study was performed using the modified Delphi method, which aims to achieve professional consensus by means of a series of questionnaires. Three different groups of items were evaluated: the beginning of antiepileptic treatment, the drug selected for initial monotherapy with respect to the type of epilepsy, and the drug selected for initial monotherapy with respect to comorbidity. RESULTS: Sixty experts completed two rounds of a questionnaire. In the first round, consensus was reached on 135 of the 194 questions analyzed. After the second round, consensus was reached on 148 items. The main findings of the survey revealed a consensus on beginning treatment after the first seizure when the EEG showed abnormalities such as generalized spike-wave discharges, when MRI demonstrated an epileptogenic brain lesion, and in elderly patients. Regarding to the antiepileptic drug selected for initial monotherapy with respect to type of epilepsy, levetiracetam and lamotrigine were recommended for generalized tonic-clonic seizures regardless of sex or age; levetiracetam was recommended for myoclonic epilepsy regardless of sex; valproic acid, ethosuximide, levetiracetam, and lamotrigine were chosen for absence epilepsy; and carbamazepine, levetiracetam, lamotrigine, and oxcarbazepine were recommended for partial epilepsy regardless of age or sex. Finally, in the evaluation of drug selection with respect to comorbidity, first-generation drugs were less recommended than second-generation drugs, which were clearly preferable. The drugs on which there was a greater consensus were levetiracetam, lamotrigine, valproic acid, and topiramate. CONCLUSIONS: There is a tendency to begin treatment after the first seizure, depending on the results of additional testing. In general, first-generation drugs are less recommended for different types of epilepsy, especially in the presence of a comorbid condition. However, the authors are conveying perceptions and opinions, the effect of which on treatment outcomes has not been evaluated.

Self-reported memory problems in everyday activities in patients with epilepsy treated with antiepileptic drugs.

OBJECTIVE: The goal of this study was to assess everyday memory complaints in a large cohort of patients with epilepsy treated with antiepileptic drugs and to determine demographic, clinical, and emotional state factors associated with patients' self-perception of memory disturbances. METHODS: This cross-sectional epidemiological study was carried out in routine clinical practice using the Questionnaire of Memory Efficiency (QME) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Six hundred sixty-one patients were recruited. The time since epilepsy diagnosis was 17.3 years (SD=12.5); the number of seizures in the past year 13.8 (SD=4.8); the proportion of patients free of seizures in the last year 42.5%; the proportion of patients with partial seizures 73.2%; and the proportion of patients on monotherapy 56.3%. Total QME score was 110.0 (SD=18.6). Depression and anxiety scores and polytherapy explained 38.7% of the QME variance. CONCLUSIONS: Subjective memory functioning in this cohort of patients with epilepsy was relatively good. Complaints expressed by these patients are explained mainly by the presence of depressive and anxiety symptoms.

Accelerated long-term forgetting in resected and seizure-free temporal lobe epilepsy patients.

Episodic memory impairments caused by temporal lobe epilepsy (TLE) are well documented in the literature. Standard clinical episodic memory tests typically include a 30-min delayed recall test. However, in the past decade, it has become apparent that this standard test does not capture the full range of memory problems in TLE patients. Some patients perform well on a standard 30-min delayed recall test, but show Accelerated Long-term Forgetting (ALF) after 24 h. Although ALF has been investigated in patients with different types of epilepsy, current research on resected TLE patients is missing. In the present study, resected TLE patients were compared to a control group matched on initial learning. They showed normal performance on verbal recall after 30 min, but impairments became apparent after one week. Moreover, the significant interaction between participant group and memory test delay demonstrated that the patients indeed showed an acceleration in forgetting. Furthermore, ALF was present in both left and right resected TLE patients, which contradicts the presence of material-specific hemispheric differences in ALF. In addition, ALF was observed in seizure-free resected TLE patients, thereby demonstrating that this factor is not crucial for long-term memory deficits. The outcome shows that clinicians are likely to underestimate memory deficits in resected TLE patients and, therefore, advocates for the inclusion of ALF tests in standard clinical batteries for both pre- and post-surgery testing sessions.

[Diagnostic challenges in epilepsy]. / Desafios diagnosticos en epilepsia.

INTRODUCTION: Epileptic seizures and epilepsy are part of daily clinical practice in neurology. Yet, the number of false positive diagnoses is surprisingly high. Almost one out of every five patients treated for epilepsy does not really have this diagnosis, which is a high percentage bearing in mind the social and medical consequences that being diagnosed with epilepsy entails. AIMS: To summarise the most important diagnostic challenges in epilepsy, to describe possible sources of diagnostic error and to offer advice on how to avoid them. DEVELOPMENT: Epilepsy is characterised by a tendency to suffer unprovoked epileptic seizures. The greatest obstacle when it comes to diagnosing a case of epilepsy is the fact that epileptic seizures are transient phenomena that occur relatively infrequently and the physician who must carry out the diagnosis will rarely see them. Moreover, there are other clinical events, such as syncopes or non-epileptic seizures, that may be similar to epileptic seizures in appearance and, consequently, can be mistaken for them. Finally, when interpreting the two most important complementary diagnostic techniques in epileptology, the electroencephalogram and magnetic resonance imaging of the brain, the most common errors must be taken into account in order to prevent mistaken diagnoses. CONCLUSIONS: The diagnosis of epilepsy is a challenge and must be based on a detailed and specific medical record. If there are any reasonable doubts, from the outset, about the diagnosis of epilepsy or if the patient does not respond well to the antiepileptic treatment, we recommend referring the patient to a specialised centre to establish a definitive diagnosis.

TITLE: Desafios diagnosticos en epilepsia.Introduccion. Las crisis epilepticas y la epilepsia son parte de la practica clinica diaria en neurologia. No obstante, el numero de diagnosticos falsos positivos es sorprendentemente alto. Casi uno de cada cinco pacientes tratado por epilepsia en realidad no tiene ese diagnostico, un porcentaje elevado teniendo en cuenta las consecuencias sociomedicas que conlleva el diagnostico de epilepsia. Objetivos. Resumir los desafios diagnosticos mas importantes en epilepsia, describir posibles fuentes de error en el diagnostico y proporcionar consejos sobre como evitarlos. Desarrollo. La epilepsia se caracteriza por una tendencia a sufrir crisis epilepticas no provocadas. El mayor obstaculo al diagnosticar una epilepsia radica en que las crisis epilepticas son fenomenos transitorios que ocurren relativamente con poca frecuencia y el medico que realiza el diagnostico raramente llega a verlas. Ademas, existen otros eventos clinicos, como por ejemplo sincopes o crisis no epilepticas, que pueden tener una apariencia similar a las crisis epilepticas y, en consecuencia, confundirse con ellas. Finalmente, al interpretar las dos tecnicas diagnosticas complementarias mas importantes en epileptologia, el electroencefalograma y la resonancia magnetica cerebral, deben tenerse en cuenta los errores mas comunes para prevenir diagnosticos erroneos. Conclusiones. El diagnostico de una epilepsia es un reto y debe basarse en una historia clinica detallada y especifica. Si desde el inicio existen dudas razonables sobre el diagnostico de epilepsia o si el paciente no responde bien al tratamiento antiepileptico, recomendamos derivar al paciente a un centro especializado que establezca un diagnostico definitivo.

Cascading processes in a changing environment: Disturbances on fluvial ecosystems in Chile and implications for hazard and risk management.

The compound hazard effects of multiple process cascades severely affect Chilean river systems and result in a large variety of disturbances on their ecosystems and alterations of their hydromorphologic regimes leading to extreme impacts on society, environment and infrastructure. The acute, neo-tectonically pre-determined susceptibility to seismic hazards, the widespread volcanic activity, the increasing glacier retreat and the continuous exposure to forest fires clearly disturb entire riverine systems and concur to trigger severe floods hazards. With the objective to refine the understanding of such cascading processes and to prospect feasible flood risk management strategies in such a rapidly changing environment we first classify the large river basins according to a set of disturbances (i.e. volcanic eruptions, earthquakes, glacier lake outburst floods, wild fires and mass movements). Then, we describe emblematic cases of process cascades which affected specific Chilean drainage basins and resulted in high losses as tangible examples of how the cascading processes may unfold in other river basins with similar characteristics. As an attempt to enrich the debate among management authorities and academia in Chile, and elsewhere, on how to sustainably manage river systems, we: a) highlight the pivotal need to determine the possible process cascades that may profoundly alter the system and b) we suggest to refine hazard and risk assessments accordingly, accounting for the current and future exposure. We advocate, finally, for the adoption of holistic approaches promoting anticipatory adaptation which may result in resilient system responses.

Strategies to detect adverse effects of antiepileptic drugs in clinical practice.

OBJECTIVE: The aim was to study the frequency and types of adverse effects (AEs) in patients treated with antiepileptic drugs (AEDs) according to the strategies used by the neurologist to detect them. METHOD: This cross-sectional epidemiological study was carried out in standard clinical practice. Two strategies were used to detect AEs: spontaneous reporting by the patient, and a checklist of possible treatment-related adverse reactions completed by the patient. RESULTS: A total of 579 patients were recruited for the study. Roughly a third (33.7%) reported AEs spontaneously, and 65.2% did so when administered the checklist. The main reason for changing medication was lack of efficacy, but significant side effects were also an important reason for modifying treatment in those patients who reported higher levels of discomfort. CONCLUSIONS: The use of an active approach is recommended for detection of AEs of AED treatment. AEs appear to have a key effect on the decision to change treatment.