Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12-month GENERAL study.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SIGNIFICANCE: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Estudio de concordancia diagnóstica en cefalea entre neurología y atención primaria / Study of the diagnostic agreement on headaches between neurology and primary care

Introducción. La cefalea como síntoma es una patología frecuente y uno de los principales motivos de consulta por parte de atención primaria. Objetivo. Analizar las características de los pacientes derivados desde atención primaria a la consulta de neurología general con cefalea o neuralgia como motivo de consulta, y la concordancia diagnóstica. Pacientes y métodos. Estudio descriptivo transversal de todos los pacientes remitidos desde atención primaria; se recogieron variables demográficas/clínicas y se compararon las hipótesis diagnósticas de atención primaria y neurología, determinando su concordancia. Resultados. Se remitieron desde atención primaria 2.514 pacientes (588 de ellos con carácter preferente); en 378 casos el motivo de la consulta fue cefalea o neuralgia (42,46 años de media; el 77,8%, mujeres). En 139 pacientes se estableció tan sólo un diagnóstico semiológico y en el resto predominaron la migraña episódica (49,79%), la cefalea tensional crónica (18,41%) y la neuralgia del trigémino (12,13%). Desde neurología, los diagnósticos más frecuentes fueron, respectivamente, 33,86%, 24,05% y 18,67%. Se obtuvo un coeficiente kappa de 0,543 (p < 0,05), compatible con una concordancia moderada al considerar sólo los pacientes remitidos desde atención primaria con un diagnóstico concreto. Conclusiones. Las cefaleas constituyen un motivo de consulta desde atención primaria muy frecuente (15%). La concordancia diagnóstica es moderada en nuestro sector sanitario, por lo que es necesario diseñar programas de formación que ayuden a perfilar los criterios de derivación al especialista y mejorar la atención a nuestros pacientes (AU)

Introduction. Headache as a symptom is a very common disease and one of the main reasons for consultation in primary care. Aim. To analyze the characteristics of patients referred from primary care to general neurology whose chief complaint was headache and/or neuralgia and diagnostic agreement. Patients and methods. Cross-sectional study of all patients referred from primary care; demographic/clinical variables were collected and diagnostic hypothesis by primary care and general neurology were compared by determining their agreement. Results. 2,514 were referred from primary care patients (588 of them on a preferential basis); in 378 cases the reason for consultation was headache and/or neuralgia (average 42.46 years; 77.8% female). In 139 patients it was established only a semiological diagnostic and other episodic migraine predominated (49.79%), chronic tension headache (18.41%) and trigeminal neuralgia (12.13%). Since general neurology, the most common diagnoses were, respectively, 33.86%, 24.05% and 18.67%. A compatible kappa coefficient of 0.543 (p < 0.05) with a moderate agreement when considering only those patients referred from primary care to a specific diagnosis was obtained. Conclusions. Headaches are a very common reason for consultation in primary care (15%). The diagnostic agreement is moderate in our health sector so it is necessary to design training programs to help outline the criteria for referral to specialists and improve care for our patients (AU)

Acetato de eslicarbazepina: una nueva alternativa en el tratamiento de las crisis focales / Eslicarbazepine acetate: a novel therapeutic alternative in the treatment of focal seizures

Resumen. La epilepsia es una de las enfermedades neurológicas más frecuentes. En los últimos años se ha incorporado a nuestras opciones terapéuticas un número muy importante de fármacos. Desde la introducción de los primeros fármacos antiepilépticos, conocidos como clásicos o convencionales, los recientemente introducidos en el mercado poseen mecanismos de acción diferentes o estructuras químicas modificadas con el objeto de proporcionar una efectividad clínica optimizada. El acetato de eslicarbazepina pertenece a este último grupo, siendo un novedoso inhibidor de los canales de sodio activados por voltaje de una sola toma diaria, con actuación selectiva en los grupos de neuronas de activación rápida. Ha sido aprobado como indicación en terapia asociada en adultos con crisis de inicio parcial, con o sin generalización secundaria. Se metaboliza ampliamente a eslicarbazepina y, en menor proporción, a R-licarbacepina y oxcarbacepina. En dosis de 800 y de 1.200 mg, ha demostrado una reducción significativa en un porcentaje elevado de pacientes con epilepsia farmacorresistente en tratamiento de forma simultánea con hasta tres fármacos antiepilépticos, y esta eficacia se mantiene en los estudios abiertos de seguimiento hasta de un año de duración. Su tolerabilidad es, por lo general, buena; la mayor parte de efectos adversos son de intensidad leve a moderada, siendo bajo el porcentaje de pacientes que retiran el tratamiento por este motivo. El acetato de eslicarbazepina constituye una alternativa de tratamiento en terapia asociada en los pacientes con epilepsia parcial que no responden de forma adecuada al tratamiento en monoterapia (AU)

Summary. Epilepsy is one of the most common neurological diseases. In recent years an important number of drugs have een added to the therapeutic options we have available to us. With the aim of offering an optimal clinical effectiveness,the mechanisms of action or chemical structures of the antiepileptic drugs recently introduced onto the market have been modified with respect to the first, so-called classical or conventional, antiepileptics. Eslicarbazepine acetate belongs to this group of recently incorporated pharmaceuticals and is a novel single daily dose voltage-gated sodium channel blocker, which acts selectively in groups of rapid-activation neurons. It has been approved for indication in associated therapy in adults with partial onset seizures, with or without secondary generalisation. It is widely metabolised to eslicarbazepine and, to a lesser extent, to R-licarbazepine and oxcarbazepine. In 800 mg and 1200 mg doses it has been shown to bring about a significant reduction in a high percentage of patients with refractory epilepsy in simultaneous treatment with up to three antiepileptic drugs, and this effectiveness is maintained in open follow-up studies lasting up to a year. It is generally speaking well-tolerated; most of the adverse side-effects range in intensity from mild to moderate, and the percentage of patients who withdraw from treatment for this reason is low. Eslicarbazepine acetate is an alternative treatment in associated therapy in patients with partial epilepsy who do not respond adequately to treatment in monotherapy (AU)

[Eslicarbazepine acetate: a novel therapeutic alternative in the treatment of focal seizures]. / Acetato de eslicarbazepina: una nueva alternativa en el tratamiento de las crisis focales.

Epilepsy is one of the most common neurological diseases. In recent years an important number of drugs have been added to the therapeutic options we have available to us. With the aim of offering an optimal clinical effectiveness, the mechanisms of action or chemical structures of the antiepileptic drugs recently introduced onto the market have been modified with respect to the first, so-called classical or conventional, antiepileptics. Eslicarbazepine acetate belongs to this group of recently incorporated pharmaceuticals and is a novel single daily dose voltage-gated sodium channel blocker, which acts selectively in groups of rapid-activation neurons. It has been approved for indication in associated therapy in adults with partial onset seizures, with or without secondary generalisation. It is widely metabolised to eslicarbazepine and, to a lesser extent, to R-licarbazepine and oxcarbazepine. In 800 mg and 1200 mg doses it has been shown to bring about a significant reduction in a high percentage of patients with refractory epilepsy in simultaneous treatment with up to three antiepileptic drugs, and this effectiveness is maintained in open follow-up studies lasting up to a year. It is generally speaking well-tolerated; most of the adverse side-effects range in intensity from mild to moderate, and the percentage of patients who withdraw from treatment for this reason is low. Eslicarbazepine acetate is an alternative treatment in associated therapy in patients with partial epilepsy who do not respond adequately to treatment in monotherapy.

Estudio comparativo de grupos independientes de pacientes con migraña episódica tratados preventivamente con flunaricina o nadolol / A study to compare independent groups of patients with episodic migraine who were treated preventively with flunarizine or nadolol

Introducción. La flunaricina, con nivel de evidencia A, y el nadolol, con nivel de evidencia C, estarían indicados como tratamiento preventivo de la migraña. No existen estudios previos que comparen la efectividad de ambos fármacos. Objetivo. Comparar parámetros de efectividad en grupos independientes de pacientes tratados preventivamente con uno de los fármacos del estudio a los que se aplicó el mismo protocolo. Pacientes y métodos. Se seleccionó a pacientes con migraña episódica (criterios de la Sociedad Internacional de Cefaleas del 2004) que se habían sometido a tratamiento preventivo por primera vez, con flunaricina (5 mg/día) o nadolol (20-40 mg/día). Se analizaron las variables principales de efectividad (reducción del número de crisis al cuarto mes de tratamiento y tasa de respondedores). Resultados. Se incluyó a 227 pacientes con intención de recibir tratamiento: 155 con flunaricina (80,5% mujeres; edad media: 38,3 ± 12,1 años) y 72 con nadolol (63,8% mujeres; edad media: 37,1 ± 12,0 años). La media de crisis en el mes previo al tratamiento fue de 6,09 ± 2,6 en el grupo de la flunaricina y de 5,1 ± 1,7 en el grupo del nadolol (p = 0,0079); la media de crisis al cuarto mes de tratamiento fue de 2,61 ± 2,4 en el grupo de la flunaricina y de 2,77 ± 2,4 en el grupo del nadolol (p = NS). Porcentaje de reducción de migrañas: 55,2% con flunaricina y 50,4% con nadolol (p = NS). La tasa de respondedores fue del 69% con flunaricina y del 67% con nadolol (p = NS). La tasa de respuesta excelente (reducción mayor o igual al 75% de las crisis) fue del 52,2% con flunaricina y del 36,1% con nadolol (p = 0,0077). Porcentaje de efectos adversos: 48,3% con flunaricina frente a 25% con nadolol (p = 0,0009). La tasa de satisfacción fue del 68%, similar en ambos grupos. Conclusión. Tanto la flunaricina como el nadolol mostraron ser efectivos en el tratamiento preventivo de la migraña episódica. La flunaricina se utilizó con mayor frecuencia en nuestro medio y fue peor tolerada (AU)

Introduction. Flunarizine, with level of evidence A, and nadolol, with evidence level C, would be indicated as preventive treatment of migraine. Yet, no previous studies have been conducted to compare the effectiveness of the two drugs. Aim. To compare the effectiveness parameters in independent groups of patients treated preventively with one of the pharmaceuticals from the study, the same protocol being applied in both cases. Patients and methods. The subjects selected for the study were patients with episodic migraine (according to 2004 International Headache Society criteria) who had undergone preventive treatment for the first time, with flunarizine (5 mg/day) or nadolol (20-40 mg/day). The main effectiveness variables (reduction in the number of seizures at four months of treatment and responder rates) were analysed. Results. The study included 227 patients who intended to receive treatment: 155 with flunarizine (80.5% females; mean age: 38.3 ± 12.1 years) and 72 with nadolol (63.8% females; mean age: 37.1 ± 12.0 years). The mean number of seizures prior to treatment was 6.09 ± 2.6 in the flunarizine group and 5.1 ± 1.7 in the nadolol group (p = 0.0079); at four months of treatment it was 2.61 ± 2.4 in the flunarizine group and 2.77 ± 2.4 in the nadolol group (p = NS). Percentage of reduction of migraines: 55.2% with flunarizine and 50.4% with nadolol (p = NS). The responder rate was 69% with flunarizine and 67% with nadolol (p = NS). The excellent response rate (reduction in the number of seizures by 75% or more) was 52.2% with flunarizine and 36.1% with nadolol (p = 0.0077). Percentage of adverse side effects: 48.3% with flunarizine and 25% with nadolol (p = 0.0009). The satisfaction rate was similar in both groups, 68%. Conclusions. Both flunarizine and nadolol proved to be effective in the preventive treatment of episodic migraine. Flunarizine is used more often in our milieu and was less well tolerated (AU)

Factores predisponentes al abandono del tratamiento preventivo en una serie de pacientes con migraña / Predisposing factors affecting drop-out rates in preventive treatment in a series of patients with migraine

Introducción. Más de un 30% de pacientes abandona el tratamiento preventivo de la migraña. Esta situación es poco conocida y los factores de riesgo que llevan al abandono del tratamiento tampoco están identificados. Objetivo. Valorar alguno de los factores que pueden predisponer al abandono de un tratamiento preventivo. Pacientes y métodos. Es un estudio prospectivo de pacientes con migraña que precisaron tratamiento preventivo por primera vez con uno de tres fármacos considerados de primera línea: un betabloqueante (nadolol), un neuromodulador (topiramato) o un antagonista del calcio (flunaricina). Se establecieron dos grupos según se produjese abandono o no del tratamiento. Se analizaron y compararon diferentes variables demográficas y clínicas en ambos grupos. Resultados. En un total de 800 pacientes con migraña que precisaron tratamiento preventivo por primera vez, hubo un 19,7% de abandonos. En el grupo que abandonó, las variables ‘edad’, ‘número de crisis previas al tratamiento preventivo’ y ‘efectos adversos’ mostraron diferencias significativas con las del grupo de pacientes que no suspendieron el tratamiento preventivo. Conclusiones. El fármaco utilizado como tratamiento preventivo, los efectos adversos, la edad más joven y el menor número de crisis antes de iniciar el tratamiento preventivo favorecieron su abandono. El tipo de migraña episódica o crónica, la presencia de abuso de fármacos y los fármacos utilizados para el tratamiento de las crisis no guardaron relación con la suspensión del tratamiento preventivo (AU)

Introduction. The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified. Aim. To evaluate some of the factors that can predispose patients to drop out of preventive treatment. Patients and methods. We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups. esults. Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables ‘age’, ‘number of seizures’, ‘number of seizures prior to preventive treatment’ and ‘side effects’ showed significant differences with those from the group of patients who did not drop out of preventive treatment. Conclusions. The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatmen (AU)

[Predisposing factors affecting drop-out rates in preventive treatment in a series of patients with migraine]. / Factores predisponentes al abandono del tratamiento preventivo en una serie de pacientes con migraña.

INTRODUCTION: The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified. AIM: To evaluate some of the factors that can predispose patients to drop out of preventive treatment. PATIENTS AND METHODS: We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol), a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups. RESULTS: Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables 'age', 'number of seizures', 'number of seizures prior to preventive treatment' and 'side effects' showed significant differences with those from the group of patients who did not drop out of preventive treatment. CONCLUSIONS: The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatment.