Association between depressive and anxious symptoms with cognitive function and quality of life in drug-resistant epilepsy.

•Depressive/anxious disorders and cognitive impairment are frequent comorbidities in epilepsy and have a more deleterious effect in DRE.•Studies concerning the relationship between anxiety and depression and cognitive performance in DRE are scarce.•Higher scores in HADS are associated with lower QOLIE-31 scores and might be considered as predictors of QOL in DRE.•A relationship between anxious and depressive symptoms -measured with HADS and SCL-90R- and cognition might not exist.•There remains an unexplored study area regarding this relationship which requires more attention to improve the assessment of DRE.

Clinical relevance of interictal dysphoric disorder and its impact on quality of life in drug-resistant epilepsy.

OBJECTIVE: This study aims to assess the prevalence of Interictal Dysphoric Disorder (IDD) in drug-resistant epilepsy (DRE) and to describe its clinical and psychopathological profile, including personality, as well as its impact on quality of life (QOL). METHOD: A retrospective cross-sectional study from an Epilepsy Unit from January 2007 to December 2017. All patients were diagnosed with DRE. Patients underwent a battery of tests (HADS, SCL-90R, PDQ-4+, QOLIE-31) and a psychiatrist assessed the presence of Axis-I disorders and IDD. Statistical procedures were carried out using R-4.0.1 software. RESULTS: A total of 282 patients were included. A statistically significant association was found between IDD and mood and anxiety disorders (p < 0.001 and p < 0.05 respectively), and between IDD and higher scores in all HADS and SCL-90-R items compared to subjects without IDD (p < 0.001). A statistically significant association was also found between IDD and obsessive-compulsive, borderline and depressive personality disorder (p < 0.05). Scores in all QOLIE-31 items except for 'medication effects' were significantly lower in subjects with IDD compared with subjects without IDD (p < 0.001). CONCLUSIONS: In DRE, IDD subjects show differences in the psychopathological profile and QOL scores compared to subjects without a diagnosis of IDD. An early diagnosis of IDD could facilitate prompt interventions which might positively impact QOL.

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.

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

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.(AU)

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.(AU)

[«Apuntes en Neurologia¼ (Notes in Neurology): a synthesis of the evidence on common paroxysmal neurological disorders and on neurodegenerative disorders]. / «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.

«Apuntes en Neurologia¼ is an initiative in which prominent national and international leaders, with broad academic recognition, came together to synthesise the most outstanding clinical aspects within their area of interest and to discuss the latest developments in a more accessible language. Understanding the factors that affect the onset and progression of any neurological disease through a review is important to be able to develop strategies to reduce the burden of these diseases. Moreover, knowledge of the clinical aspects is essential to solve the problems of daily clinical practice. The data collected here reflect the weight of evidence and some of them anticipate a promising future in the treatment of these diseases. This first edition focuses on common paroxysmal neurological disorders such as migraine, epilepsy and sleep disorders, as well as neurodegenerative disorders such as Parkinson's disease and cognitive impairment. These are clearly different pathologies, although some of them such as migraine and epilepsy, may share clinical symptoms. Sleep disorders, however, are important manifestations of neurodegenerative diseases that are sometimes clinically apparent long before the onset of other neurological symptoms. After recalling pathophysiology and diagnosis, the current review focuses on bringing together the main advances in five of the major neurological diseases.

TITLE: «Apuntes en Neurologia¼: una sintesis de la evidencia en trastornos neurologicos comunes paroxisticos y en trastornos neurodegenerativos.«Apuntes en Neurologia¼ es una iniciativa en la cual lideres de primera linea nacional e internacional, con amplio reconocimiento academico, se reunieron para sintetizar los aspectos clinicos mas destacables dentro de su area de interes y acercar las novedades en una lengua mas proxima. Entender los factores que afectan al inicio y progresion de cualquier enfermedad neurologica a traves de una revision es importante para el desarrollo de estrategias en pro de reducir la carga de estas enfermedades, y conocer los aspectos clinicos es esencial para poder resolver los problemas de la practica clinica diaria. Los datos aqui recogidos reflejan el peso de la evidencia y algunos de ellos anticipan un futuro prometedor en el tratamiento de estas enfermedades. Esta primera edicion se centra en trastornos neurologicos comunes paroxisticos como la migraña, la epilepsia y las alteraciones del sueño, y en trastornos neurodegenerativos como la enfermedad de Parkinson y el deterioro cognitivo. Se trata de patologias claramente diferentes, si bien algunas de ellas, como la migraña y la epilepsia, pueden compartir sintomatologia clinica. Los trastornos del sueño, por su parte, son manifestaciones importantes de enfermedades neurodegenerativas que, en ocasiones, son clinicamente evidentes mucho antes del inicio de otros sintomas neurologicos. Tras recordar la fisiopatologia y el diagnostico, la revision actual se centra en acercar los principales avances en cinco de las principales enfermedades neurologicas.

[Results of vagal nerve stimulation in patients with pharmacoresistant epilepsy in a national epilepsy referral centre]. / Resultados de la estimulacion del nervio vago en pacientes con epilepsia farmacorresistente en un centro de referencia nacional de epilepsia.

AIM: To describe clinical results and complications derived from vagal nerve stimulation therapy in drug resistant epileptic patients unsuitable for other surgical treatments, since the first implant in an epilepsy national referral centre. PATIENTS AND METHODS: A retrospective analysis of the patients implanted in our centre was held. Data related to baseline characteristics of their epilepsy and therapy complications was collected. RESULTS: 32 new implants in 31 patients are included, mean age of 34 years, 29.3 years of disease evolution, three anti-epileptic drugs at surgery and a postoperative follow-up of 4.03 years. Complex partial seizures types (71.9%) and cryptogenic aetiology (59.4%) were the most frequent. 75% of patients hadn't history of previous epilepsy surgery. 43.8% of patients had a seizure frequency improvement above 50%, with a better response in patients with complex partial seizures (p = 0.22) and cryptogenic aetiology. None statistical significance was found between antiepileptic drugs and seizure frequency. Dysphonia, hoarseness and dysphagia, mostly transient, were the side effects registered. There was an asystole during surgery, completely recovered. One device was replaced due to hardware rupture after a seizure related trauma, one had to be adjusted due to a previous vocal cord paresis, and one dysfunctioning device was removed. In 84.4% the tolerance was excellent. CONCLUSIONS: Vagal nerve stimulation is an effective treatment for significant seizure frequency improvement of resistant patients untreatable with other medical or surgical treatments. Further studies are needed to predict the individual response of each patient to therapy and optimizing indications, therefore contributing to cost/benefit optimization.

TITLE: Resultados de la estimulacion del nervio vago en pacientes con epilepsia farmacorresistente en un centro de referencia nacional de epilepsia.Objetivos. Describir los resultados clinicos y complicaciones derivados de la estimulacion vagal en pacientes con epilepsia farmacorresistente no tributaria de otras modalidades de tratamiento quirurgico, desde el primer implante en un centro de referencia nacional. Pacientes y metodos. Se realizo un analisis retrospectivo de los pacientes implantados en nuestro centro y se extrajeron datos relativos a las caracteristicas basales de su epilepsia y complicaciones derivadas. Resultados. Se incluyeron 32 nuevos implantes en 31 pacientes, con una edad media de 34 años, evolucion de enfermedad de 29,3 años, tres farmacos antiepilepticos prequirurgicos y 4,03 años de seguimiento. Las crisis parciales complejas (71,9%) y criptogenicas (59,4%) fueron el tipo y la etiologia de crisis mas frecuentes. El 75% no tenia antecedentes quirurgicos de epilepsia. Un 43,8% presento mejoria igual o superior al 50%, mayor en las epilepsias parciales complejas (p = 0,22) y la etiologia criptogenica. No se hallo asociacion estadistica entre ajustes de medicacion y frecuencia de las crisis. Los efectos secundarios encontrados fueron disfonia, ronquera y disfagia transitorias, y una asistolia intraoperatoria recuperada. Se realizo un recambio por ruptura de hardware postraumatica. Un paciente con paresia preexistente de cuerda vocal presento estridor laringeo que requirio ajuste de intensidad, y se produjo una retirada del sistema por disfuncion. En el 84,4%, la tolerancia fue excelente. Conclusiones. Constituye un tratamiento efectivo para mejorar significativamente la frecuencia de crisis de los pacientes farmacorresistentes y con contraindicacion para otras modalidades de tratamiento quirurgico. Se precisan futuros estudios para predecir la respuesta individual de cada paciente, optimizar las indicaciones y mejorar la relacion coste/beneficio.

Epilepsia resistente a fármacos. Concepto y alternativas terapéuticas / Drug-resistant epilepsy: Definition and treatment alternatives

Introducción: El dolor es un síntoma muy frecuente en los pacientes con síndrome de Guillain-Barré, con una intensidad de moderada a severa en la mayoría de los casos; puede persistir luego de la resolución de la enfermedad. Objetivo: Identificar la terapia analgésica más apropiada para el manejo del dolor en los pacientes con síndrome de Guillain-Barré. Material y métodos: Se realizó una búsqueda y selección sistemática de los artículos científicos sobre el tratamiento del dolor en pacientes con síndrome de Guillain-Barré publicados entre enero de 1985 y diciembre de 2012. Se incluyeron solo ensayos clínicos aleatorizados, doble ciego, que evaluaron el efecto de los medicamentos en el tratamiento del dolor en estos pacientes. Resultados: Cuatro artículos cumplieron los criterios de inclusión. Uno evaluó el uso de gabapentina, otro, el de carbamazepina, otro comparó el uso de gabapentina y carbamazepina, y el último evaluó el uso de metilprednisolona. Tanto carbamazepina como gabapentina fueron útiles en el manejo del dolor. En el estudio que comparó carbamazepina y gabapentina, los pacientes presentaron menor intensidad del dolor con el uso de este último. La metilprednisolona no mostró un efecto positivo en la reducción del dolor. Los datos publicados no permitieron la realización de un metaanálisis. Conclusiones: No hay evidencia sólida en el momento actual para recomendar una opción terapéutica específica ante este problema. Es necesaria la realización de futuros estudios clínicos que incluyan un mayor número de pacientes, por un tiempo más prolongado, que individualicen los tipos de dolor por pacientes y midan objetivamente la intensidad de este

Introduction: Pain is a common symptom in patients with Guillain-Barre syndrome. Intensity is moderate to severe in most cases and pain may persist after resolution of the disease. Objective: Identify the most appropriate analgesic therapy for pain management in patients with Guillain-Barre syndrome. Material and methods: Systematic review and selection of scientific articles on treatment of pain in Guillain-Barre syndrome patients, published between January 1985 and December 2012. We included only randomised, double-blind, controlled trials assessing the effectiveness of drugs for pain management in these patients. Results: Four articles met the inclusion criteria. One evaluated the use of gabapentin, another evaluated carbamazepine, a third compared gabapentin to carbamazepine, and the last evaluated use of methylprednisolone. Both carbamazepine and gabapentin were useful for pain management. Patients experienced lower-intensity pain with gabapentin treatment in the study comparing that drug to carbamazepine. Methylprednisolone was not shown to be effective for reducing pain. The published data did not permit completion of a meta-analysis. Conclusions: There is no robust evidence at present that would point to a single treatment option for this disorder. Further clinical studies of larger patient samples and with a longer duration are needed to characterise types of pain for each patient and measure pain intensity in an objective way

Drug-resistant epilepsy: definition and treatment alternatives.

INTRODUCTION: Drug-resistant epilepsy affects 25% of all epileptic patients, and quality of life decreases in these patients due to their seizures. Early detection is crucial in order to establish potential treatment alternatives and determine if the patient is a surgical candidate. DEVELOPMENT: PubMed search for articles, recommendations published by major medical societies, and clinical practice guidelines for drug-resistant epilepsy and its medical and surgical treatment options. Evidence and recommendations are classified according to the criteria of the Oxford Centre for Evidence-Based Medicine (2001) and the European Federation of Neurological Societies (2004) for therapeutic actions. CONCLUSIONS: Identifying patients with drug-resistant epilepsy is important for optimising drug therapy. Experts recommend rational polytherapy with antiepileptic drugs to find more effective combinations with fewer adverse effects. When adequate seizure control is not achieved, a presurgical evaluation in an epilepsy referral centre is recommended. These evaluations explore how to resect the epileptogenic zone without causing functional deficits in cases in which this is feasible. If resective surgery is not achievable, palliative surgery or neurostimulation systems (including vagus nerve, trigeminal nerve, or deep brain stimulation) may be an option. Other treatment alternatives such as ketogenic diet may also be considered in selected patients.

[An observational study of the patterns of carbamazepine and oxcarbazepine utilisation in adult patients with partial epilepsy in Spain]. / Estudio observacional de los patrones de utilizacion de carbamacepina y oxcarbacepina en pacientes adultos con epilepsia parcial en Espana.

INTRODUCTION: The health outcomes research methodology is especially important for evaluating therapeutic efficiency and effectiveness in the case of patients with epilepsy. AIM: To describe the patterns of utilisation of carbamazepine and the new antiepileptic drug oxcarbazepine, as well as their relation with the quality of life (patient's satisfaction and social and occupational repercussion) and therapeutic efficiency (utilisation of health care resources). PATIENTS AND METHODS: We performed an observational study of 284 adult patients with partial epilepsy that was clinically controlled with carbamazepine or oxcarbazepine either in monotherapy or with the addition of some other pharmaceutical agent. The study was carried out using the Morisky-Green questionnaire (for therapeutic compliance), the Sheehan Disability Scale (SDS, social functioning) and direct questioning (patient satisfaction); therapeutic efficiency was assessed with the register of medical visits, complementary examinations and concomitant treatments. RESULTS: The study showed that 65.6% suffered from partial seizures of a single type (simple, complex or with secondary generalisation) and 34.4% had several types of seizures. Oxcarbazepine treatment was being administered to 52% (mean dose: 1134.4 mg/day) and 48% were receiving carbamazepine (mean dose: 876.3 mg/day). The SDS scores were: occupational: 2.1; social: 2.0; and familial: 1.4. Most of the patients admitted having skipped some doses under certain circumstances; for this reason, 98.9% of them presented a medium level of compliance. It was found that 8.5% of patients visited the emergency department and 3% used hospitalisation services. CONCLUSIONS: The doses of oxcarbazepine tended to be lower than those recommended on the patient information leaflet. Patients only consider themselves to be mildly affected in their social and occupational relations and are satisfied with the control of their seizures. Patients receiving combination therapy utilise more health care resources.

Estudio observacional de los patrones de utilización de carbamacepina y oxcarbacepina en pacientes adultos con epilepsia parcial en España / An observational study of the patterns of carb amazepine and oxcarbazepine utilisation in adult patients with partial epilepsy in Spain

La metodología de la investigación de resultados en salud es particularmente importante para evaluarla efectividad y la eficiencia terapéutica en el caso de pacientes con epilepsia. Objetivo. Describir los patrones de utilización de la carbamacepina y del nuevo fármaco antiepiléptico oxcarbacepina, y su relación con la calidad de vida (satisfacción del paciente y repercusión sociolaboral) y la eficiencia terapéutica (utilización de recursos sanitarios). Pacientes y métodos. Estudio observacional de 284 pacientes adultos con epilepsia parcial clínicamente controlada con carbamacepina u oxcarbacepina en monoterapia o con otro fármaco añadido. Se utilizaron el cuestionario de Morisky-Green (cumplimiento terapéutico), el cuestionario de incapacidad de Sheehan (SDS, funcionamiento social) y preguntas directas (satisfacción del paciente); la eficiencia terapéutica se evaluó con el registro de visitas médicas, exploraciones complementarias y tratamientosconcomitantes. Resultados. El 65,6% padecía crisis parciales de un solo tipo (simples, complejas o con generalización secundaria) y el 34,4%, varios tipos de crisis. El 52% estaba en tratamiento con oxcarbacepina (dosis media: 1.134,4 mg/día) y el 48% con carbamacepina (dosis media: 876,3 mg/día). Las puntuaciones del SDS son: laboral: 2,1; social: 2,0; y familiar:1,4. La mayoría de los pacientes reconoce dejar alguna toma en determinadas circunstancias; por ello, el 98,9% presenta un nivel de cumplimiento medio. Un 8,5% de los pacientes utilizó los servicios de urgencias y un 3% utilizó los servicios de hospitalización.Conclusiones. Las dosis de oxcarbacepina tienden a ser inferiores a las recomendadas en la ficha técnica. Lospacientes sólo se consideran levemente afectados en sus relaciones sociolaborales y están satisfechos con el control de sus crisis. Los pacientes en politerapia utilizan más recursos sanitarios

The health outcomes research methodology is especially important for evaluating therapeutic efficiencyand effectiveness in the case of patients with epilepsy. Aim. To describe the patterns of utilisation of carbamazepine and the new antiepileptic drug oxcarbazepine, as well as their relation with the quality of life (patient’s satisfaction and social andoccupational repercussion) and therapeutic efficiency (utilisation of health care resources). Patients and methods.We performed an observational study of 284 adult patients with partial epilepsy that was clinically controlled with carbamazepine oroxcarbazepine either in monotherapy or with the addition of some other pharmaceutical agent. The study was carried out using the Morisky-Green questionnaire (for therapeutic compliance), the Sheehan Disability Scale (SDS, social functioning) and direct questioning (patient satisfaction); therapeutic efficiency was assessed with the register of medical visits, complementary examinations and concomitant treatments. Results. The study showed that 65.6% suffered from partial seizures of a single type(simple, complex or with secondary generalisation) and 34.4% had several types of seizures. Oxcarbazepine treatment was being administered to 52% (mean dose: 1134.4 mg/day) and 48% were receiving carbamazepine (mean dose: 876.3 mg/day).The SDS scores were: occupational: 2.1; social: 2.0; and familial: 1.4. Most of the patients admitted having skipped some doses under certain circumstances; for this reason, 98.9% of them presented a medium level of compliance. It was found that 8.5% ofpatients visited the emergency department and 3% used hospitalisation services. Conclusions. The doses of oxcarbazepine tended to be lower than those recommended on the patient information leaflet. Patients only consider themselves to be mildlyaffected in their social and occupational relations and are satisfied with the control of their seizures. Patients receiving combination therapy utilise more health care resources