Effect of Cenobamate on Cognition in Patients with Drug-Resistant Epilepsy with Focal Onset Seizures: An Exploratory Study.

BACKGROUND AND OBJECTIVE: Most second and third generation antiseizure medications (ASMs) are associated with cognitive adverse events, which are a major concern for patients. However, the profile of cognitive adverse events differs between ASMs. This study investigated the effects of cenobamate on cognition in patients with drug-resistant epilepsy (DRE) within the Spanish Expanded Access Program (EAP). METHODS: This was a retrospective, observational study. Inclusion criteria were age ≥ 18 years, DRE with focal seizures, and availability of cognition assessments and EAP authorization. Data were sourced from the clinical records of patients who took part in the Spanish cenobamate EAP. Primary endpoints included cognition (based on 20 neuropsychological outcomes, including verbal and visuospatial episodic memory, verbal fluency, executive function, working memory, attention, and speed of processing), seizure frequency, and concomitant antiseizure medication (ASM) usage at 6 months. RESULTS: The study included 20 patients; 10 patients (50%) had daily seizures, 7 (35%) had weekly seizures and 3 (15%) had monthly seizures. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 10 and 3, respectively. Mean cenobamate doses were 12.5 mg/day at baseline and 191.2 mg/day at 6 months. There was a statistically significant improvement in cognitive scores between baseline and 6 months for two measures of verbal episodic memory (p = 0.0056 and p = 0.0013) and one measure of visuospatial episodic memory (p = 0.011), and a significant worsening in cognitive score for attention (p = 0.030). At 6 months, 14 patients (70%) had a ≥ 50% reduction in seizure frequency, 3 patients (15%) had a ≥ 90% reduction, and 1 patient (5%) was seizure free. There were significant decreases in the mean number of concomitant ASMs (p = 0.0009), the sum of the ratios of prescribing daily dose/daily defined dose (total ratio of DDD) for concomitant ASMs (p < 0.0001), and concomitant ASM drug load (p = 0.038) between baseline and 6 months. Total ratio of DDD was significantly lower at 6 months for perampanel (p = 0.0016), benzodiazepines (p = 0.035), and sodium channel blockers (p = 0.0005) compared with baseline. Based on analysis of covariance, cognitive tests related to verbal or visuospatial episodic memory (e.g., RT of FCSRT, or ROCFT), executive functions (e.g., TMT-B), and processing speed (some 5-Digit Test subtests) appeared to be closely related to the reduction in pharmacological burden rather than the improvement in seizure control. CONCLUSIONS: Significant improvements in cognition, seizure frequency, and concomitant ASM usage were observed after the introduction of cenobamate in patients with DRE in a real-world setting. Covariance analysis supports the reduction in concomitant ASMs as the most important factor driving cognitive improvements with cenobamate. As this was an exploratory study with an uncontrolled, retrospective design and a low number of patients, further studies are required to confirm the findings.

Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry.

Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient's journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country.

Cenobamate and Clobazam Combination as Personalized Medicine in Autoimmune-Associated Epilepsy With Anti-Gad65 Antibodies.

BACKGROUND AND OBJECTIVES: Autoimmune-associated epilepsy (AAE) with antiglutamic acid decarboxylase 65 (GAD65) antibodies is considered a T-cell-mediated encephalitis that evolves to drug-resistant epilepsy. We do not have an effective therapeutic strategy for these patients. Because the GAD enzyme is primarily responsible for the conversion of glutamate to GABA, the mechanism of epileptogenesis in this condition predicts decreased levels of GABA content in synaptic vesicles. Cenobamate (CNB) acts as a positive allosteric modulator at synaptic and extra synaptic GABAA receptors, producing increased inhibitory neurotransmission in the brain. This mechanism could be especially beneficial in AAE with anti-GAD65 antibodies because it would be able to correct the imbalance due to the GABAergic stimulation deficit in postsynaptic neurons. METHODS: We recruit a retrospective multicentric consecutive case series of AAE with anti-GAD65 antibodies from 5 epilepsy units in Spain who have received treatment with CNB. RESULTS: A total of 8 patients were recruited. This cohort of highly refractory patients have failed a mean of 9.50 (SD = 3.20) ASM without control of seizures for sustained periods of time. The average number of seizures per month during the previous 3 months before CNB treatment was 19.63 (SD = 17.03). After the introduction of CNB improvement was achieved in all our patients, with a median reduction in the number of seizures of 92.22% (interquartile range [IQR]: 57.25-98.75). The mean follow-up was 156.75 days (SD = 68.23). In patients with concomitant treatment with clobazam (CLB), the median percentage of seizure reduction was higher than those not taking CLB: 94.72% (IQR: 87.25-100) vs 41.50% (p = 0.044) and also higher than the control group of patients with refractory epilepsy not related to anti-GAD65 treated with the same combination: 94.72% (IQR: 87.25-100) vs 45.00% (IQR: 25.00-87.00) (p = 0.019). DISCUSSION: Treatment with the combination CNB + CLB could be a type of personalized medicine in patients with AAE with anti-GAD65. Our preliminary data will need to be endorsed with new prospective and controlled studies.

Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies.

Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

Case Report: Autoimmune Psychosis in Chromosome 22q11.2 Deletion Syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is characterized by congenital cardiac abnormalities, hypoplastic thymus, palatal abnormalities, and hypocalcemia, although other clinical features are frequent such as autoimmune and psychiatric disorders. One-third of the patients have psychotic disorders, frequently followed by developmental regression and long-term cognitive disturbances. Despite humoral and cellular immunodeficiency are common in 22q11DS, it is associated with an increased prevalence of autoimmune disorders such as idiopathic thrombocytopenic purpura and juvenile idiopathic arthritis, likely due to immune dysregulations associated with thymic abnormalities, which plays a major role in self-tolerance. We report an unique case of a 14-year-old girl with 22q11DS that presented with subacute psychotic symptoms, intolerance to antipsychotics, CSF pleocytosis, and EEG abnormalities, that was successfully treated with empiric immunotherapy after fulfilling criteria for probable seronegative autoimmune encephalitis and probable autoimmune psychosis. The autoimmune etiology of these clinical features of 22q11DS has never been postulated despite the predisposition of this syndrome to present autoimmune disorders. We suggest the systematic evaluation with serum and CSF neuronal antibodies, MRI, and EEG of patients with 22q11DS that develop subacute psychotic symptoms or rapidly progressive cognitive decline. Early immunomodulatory therapies should be carefully considered if criteria of probable autoimmune psychosis or possible autoimmune encephalitis are fulfilled, as it may prevent long-term disabilities. Further studies are required to assess the autoimmune origin of psychosis and cognitive impairment associated with 22q11DS.

Prevalence of Neural Autoantibodies in Paired Serum and Cerebrospinal Fluid in Adult Patients with Drug-Resistant Temporal Lobe Epilepsy of Unknown Etiology.

In order to determine the prevalence of neural autoantibodies in adult patients with drug-resistant temporal lobe epilepsy (DRTLE) of unknown etiology, we compared the characteristics of patients with and without autoantibodies and applied antibody predictive scores to the patients. Patients aged ≥18 years with DRTLE of unknown etiology and ≥12 months of evolution were prospectively recruited. Neural autoantibodies in serum and CSF were systematically determined in all patients. We created the ARTE (antibody in drug-resistant temporal lobe epilepsy) score based on the variables associated with the presence of neural autoantibodies. Twenty-seven patients were included. The mean (SD) age in years at the index date was 52 (±14.2) and at epilepsy onset was 32 (±17.1). The mean epilepsy duration was 19 (±12.5) years. Neural autoantibodies were detected in 51.85% (14/27) of patients. The presence of bitemporal, independent, interictal epileptiform discharges (BIIED) had a higher frequency in patients with neural autoantibodies (57.1% vs. 15.4%; p = 0.025) as well as those patients with a previous history of status epilepticus (49.2% vs. 0.0%; p = 0.007). The ARTE score showed an area under the curve (AUC) of 0.854. Using a cut-off point of ≥1, the sensitivity was 100% and the specificity was 46.1%, whereas when using a cut-off point of ≥3, the results were 35.7% and 100%, respectively. We found a high prevalence of neural autoantibodies in patients with DRTLE of unknown etiology, indicating an autoimmune mechanism. The presence of BIIED and a history of SE in DRTLE of unknown etiology are possible markers for autoimmune-associated epilepsy. The proposed ARTE score requires future validation in larger independent cohorts.

Prevalence of Neural Autoantibodies in Epilepsy of Unknown Etiology: Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of neural autoantibodies in epilepsy of unknown etiology varies among studies. We aimed to conduct a systematic review and meta-analysis to determine the pooled global prevalence and the prevalence for each antibody. METHODS: A systematic search was conducted for studies that included prospectively patients ≥16 years old with epilepsy of unknown etiology and systematically determined neural autoantibodies. A meta-analysis was undertaken to estimate pooled prevalence in total patients with a positive result for at least one neural autoantibody in serum and/or cerebrospinal fluid (CSF) and for each autoantibody. RESULTS: Ten of the eleven studies that met the inclusion criteria and a total of 1302 patients with epilepsy of unknown etiology were included in themeta-analysis. The global pooled prevalence (IC95%) was 7.6% (4.6-11.2) in a total of 82 patients with a positive result for any neural autoantibody. None of the controls available in the studies had a positive result. Individual pooled prevalence for each autoantibody was: glycine receptor (GlyR) (3.2%), glutamic acid decarboxylase (GAD) (1.9%), N-methyl-d-aspartate receptor (NMDAR) (1.8%), leucine-rich glioma inactivated-1 protein (LGI1) (1.1%), contactin-2-associated protein (CASPR2) (0.6%) and onconeuronal (0.2%). CONCLUSIONS: The pooled prevalence of neural autoantibodies in patients with epilepsy of unknown etiology is small but not irrelevant. None of the controls had a positive result. There was high heterogeneity among studies. In the future, a homogeneous protocol for testing neural autoantibodies is recommended.

Neurosarcoidosis: análisis de una serie de 20 pacientes / Neurosarcoidosis: Analysis of a series of 20 patients

INTRODUCCIÓN: La neurosarcoidosis es una rara complicación de la sarcoidosis. Existen series cortas de pacientes con esta afectación. En España son prácticamente inexistentes. Planteamos realizar un estudio retrospectivo sobre neurosarcoidosis en el Hospital Virgen de la Victoria a lo largo de 10 años. PACIENTES Y MÉTODOS: Búsqueda en la base de datos hospitalaria de los pacientes con este diagnóstico en los últimos 10 años. RESULTADOS: Ciento veinte pacientes con sarcoidosis, de los cuales 20 pacientes compatibles con neurosarcoidosis probable: el 30% fue inicio de la enfermedad, el 55% ya estaban diagnosticados de sarcoidosis y el 15% tuvieron neurosarcoidosis aislada. El 40% presentaron polineuropatía, el 15% neuropatía craneal, el 15% miopatía y el 10% focalidad del sistema nervioso central. Otros: Cefalea, mielitis, crisis epiléptica y cuadro confusional. Se trataron con esteroides, y a veces se asociaron otros inmunosupresores. El 72% de los casos se estabilizaron o hubo mejoría. Por tanto, la prevalencia de neurosarcoidosis en nuestro hospital es del 11%, parecido a otras series publicadas, con características similares, pero con mayor frecuencia de polineuropatía. El pronóstico de la enfermedad es aceptablemente favorable con tratamiento, por lo que es importante el diagnóstico precoz

INTRODUCTION: Neurosarcoidosis is a rare complication of sarcoidosis. There are small series on the condition and very few from Spain. We conducted a retrospective study of neurosarcoidosis in Virgen de la Victoria Hospital over the last 10 years. PATIENTS AND METHOD: the medical records of patients diagnosed with sarcoidosis in our setting in the last 10 years were reviewed. RESULTS: One hundred twenty patients with sarcoidosis, 20 patients with probable neurosarcoidosis: 30% at the beginning of the illness, 55% later, 15% had isolated neurosarcoidosis. Forty percent had polyneuropathy, 15% cranial neuropathy, 15% myopathy, 10% hemispheric symptoms. Others: headache, myelitis, seizures, confusional syndrome. They were treated with steroids, some of them with immunosuppressive treatment. Seventy-two percent improved or were stabilized. Therefore, neurosarcoidosis prevalence in our hospital was 11%, similar to other published series, with similar features, but polyneuropathy was more frequent. Early diagnosis is very important as prognosis is favourable with treatment

Neurosarcoidosis: Analysis of a series of 20 patients. / Neurosarcoidosis: análisis de una serie de 20 pacientes.

INTRODUCTION: Neurosarcoidosis is a rare complication of sarcoidosis. There are small series on the condition and very few from Spain. We conducted a retrospective study of neurosarcoidosis in Virgen de la Victoria Hospital over the last 10 years. PATIENTS AND METHOD: the medical records of patients diagnosed with sarcoidosis in our setting in the last 10 years were reviewed. RESULTS: One hundred twenty patients with sarcoidosis, 20 patients with probable neurosarcoidosis: 30% at the beginning of the illness, 55% later, 15% had isolated neurosarcoidosis. Forty percent had polyneuropathy, 15% cranial neuropathy, 15% myopathy, 10% hemispheric symptoms. OTHERS: headache, myelitis, seizures, confusional syndrome. They were treated with steroids, some of them with immunosuppressive treatment. Seventy-two percent improved or were stabilized. Therefore, neurosarcoidosis prevalence in our hospital was 11%, similar to other published series, with similar features, but polyneuropathy was more frequent. Early diagnosis is very important as prognosis is favourable with treatment.

Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON).

OBJECTIVE: Perampanel (PER) has been shown to be effective as an adjunctive therapy for controlling refractory focal-onset seizures (FOS). However, the information as early add-on for the treatment of FOS in the clinical practice is still scarce and must be further assessed. METHODS: An observational prospective study was conducted to evaluate the effectiveness of early add-on PER, assessed as 50% responders (seizure frequency reduced by at least 50% during the last 3 months as compared with baseline) rate at 6 and 12 months, in patients with FOS in the routine clinical practice of Spain. RESULTS: One hundred and thirteen patients (mean age: 40.3 years, 51.3% male) with FOS received PER as early add-on (1st add-on: 37.2% and 2nd: 62.8%) for a mean exposure of 11 months (mean PER dose: 6.3 mg/day at month 12). At 6 months, 50.4% and 20.4% of the patients were responders and seizure-free (respectively) relative to baseline (3 months prior to PER initiation), and at 12 months, 68.1% and 26.5% of the patients were responders and seizure-free (respectively), relative to baseline (3 months prior to PER initiation). The retention rate at 6 and 12 months was 83.2% and 80.5%, respectively. The percentage of seizure-free patients at 12 months was significantly (p = 0.033) higher when PER was added as first vs. second add-on. The number of concomitant antiepileptic drugs (AEDs) was significantly reduced from baseline to 6 and 12 months (p = 0.001). Treatment was simplified in 23.9% of patients at the end of the observation period. Drug-related adverse events (AEs), most mild or moderate, were reported in 30.1% of patients, with irritability (8%) and dizziness (7.1%) as the most frequent ones. CONCLUSIONS: This is the first observational, prospective study to evaluate efficacy and safety of early adjunctive treatment with PER in patients with focal epilepsy at 12 months. Perampanel demonstrated a good efficacy and safety profile when used at a median dose of 6 mg/day, regardless of the combination with other AEDs. Adverse events were mild or moderate, with dizziness being the most frequent one.

Epidemiología de la epilepsia en España y Latinoamérica / Epidemiology of epilepsy in Spain and Latin America

Introducción. La conexión entre España y Latinoamérica en los últimos cinco siglos ha sido muy importante desde el punto de vista cultural, étnico y comercial, lo que justifica la existencia de una identidad común que puede condicionar la epidemiología de enfermedades crónicas con determinantes genéticos y medioambientales, como la epilepsia. En los últimos quince años se han producido cambios significativos en el desarrollo económico y de condiciones sanitarias en estos países, así como flujos migratorios entre ellos que pueden haber variado la situación epidemiológica previa. Planteamos una revisión exhaustiva de los estudios de epidemiología descriptiva de la epilepsia en España y Latinoamérica. Desarrollo. Búsqueda bibliográfica de los estudios de epidemiología descriptiva sobre epilepsia en España y cada uno de los países de Latinoamérica. Se revisan su metodología y su calidad, y se extraen los datos de prevalencia e incidencia por país. Se evalúan 796 estudios, de los cuales 55 (48 de prevalencia y siete de incidencia) cumplen los requisitos de inclusión. Conclusiones. No existe evidencia de una variación de la situación epidemiológica de la epilepsia en Latinoamérica. Siguen existiendo tasas de prevalencia e incidencia mas altas que en los países occidentales. Esta diferencia es especialmente evidente en países endémicos para cisticercosis y está inversamente relacionada con la riqueza del país medida por el producto interior bruto per capita. No existe evidencia de cambio en la epidemiología de la epilepsia en España a pesar de los flujos migratorios de países con alta prevalencia de epilepsia en los últimos años

Introduction. The connection between Spain and Latin America on the cultural, ethnic and commercial levels has been very important over the last five centuries, and this accounts for the existence of a common identity that can condition the epidemiology of chronic diseases with genetic and environmental determinants, such as epilepsy. In the last 15 years significant changes have come about in the economic development and the healthcare conditions in these countries as well as the migratory flows among them that may have brought about changes in the previous epidemiological situation. We present an exhaustive review of the epidemiological studies describing the status of epilepsy in Spain and Latin America. Development. A bibliographic search was conducted of descriptive epidemiology studies about epilepsy in Spain and in each of the countries of Latin America. The methodology and quality of each study are reviewed and data on prevalence and incidence are extracted for each country. A total of 796 studies are evaluated, of which 55 (48 on prevalence and seven on incidence) meet eligibility criteria. Conclusions. There is no evidence of a variation in the epidemiological situation of epilepsy in Latin America. Some prevalence and incidence rates are still higher than in western countries. This difference is especially apparent in countries where cysticercosis is endemic and is inversely proportional to the wealth of the country, measured by the per capita gross domestic product. There is no evidence of any change in the epidemiology of epilepsy in Spain despite the migratory flows of countries with a high prevalence of epilepsy in recent years

Epidemiological study of mortality in epilepsy in a Spanish population.

PURPOSE: Studies concerning mortality in epilepsy have been performed primarily in Northern-Central Europe and US. The aim of this study was to provide information about mortality in people with epilepsy in Southern European countries. METHOD: We studied a Spanish prevalence and incidence cohort of 2309 patients aged ≥14 years with epilepsy who were treated in an outpatient epilepsy clinic between 2000 and 2013. The deceased were identified through Civil Registries. Causes of death were determined using death certificates, forensic autopsies, hospital reports, family practitioners, and care-givers' records. Standardised mortality ratios (SMRs) were calculated. RESULTS: In a total of 15,865 person-years of follow-up, 152 patients died, resulting in an SMR of 2.11 (95% CI 1.79-2.47), which was higher for those aged 14-24. There was also a high rate of death for symptomatic epilepsies, progressive causes (SMR=6.12, CI 3.50-9.94), and remote causes (SMR=2.62, CI 2.12-3.21). High SMRs were found for all kinds of epilepsy and for respiratory and tumoural causes. Patients who died of epilepsy itself were 12.5%. Sudden unexpected death in epilepsy incidence was 0.44:1000. Death from status epilepticus incidence was 20:100,000. SMRs for external causes were of no statistical significance. CONCLUSIONS: This is the first epidemiological study to examine rate of mortality in epilepsy in a Southern European country. The identified mortality pattern is similar to the one provided by researchers from developed countries. The similarities between our results concerning epilepsy-related deaths and those provided by population-based studies are the result of the scarcely selected character of our study cohort.

Control de la epilepsia en pacientes adultos con esclerosis tuberosa / Control of epilepsy in adult patients with tuberous sclerosis

Introducción. La esclerosis tuberosa es una enfermedad genética cuyas manifestaciones principales son la formación de tumores neuroectodérmicos, que asocia epilepsia secundaria muy frecuentemente. Objetivo. Describir el perfil epiléptico, el control, la frecuencia de crisis y la efectividad del tratamiento en pacientes adultos con esclerosis tuberosa. Pacientes y métodos. Estudio descriptivo en el que se han incluido pacientes adultos (mayores de 14 años) con diagnóstico confirmado de esclerosis tuberosa. Se ha analizado la frecuencia y tipos de crisis. Se ha realizado un estudio y contabilización de los diferentes fármacos antiepilépticos en cada paciente, la frecuencia de uso de cada principio activo y un estudio comparativo entre control de crisis y tipo de terapia. Resultados. De 19 adultos estudiados, tuvieron crisis epilépticas 16 (84%). Presentaron control de crisis completo, crisis esporádicas y crisis frecuentes el 44%, 25% y 31%, respectivamente. Hubo frecuencia de crisis focales, generalizadas y ambas en el 38%, 6% y 25%, respectivamente. Estaban en tratamiento con fármacos antiepilépticos en monoterapia, biterapia y triterapia el 38%, 44% y 19%, respectivamente. El más consumido globalmente fue el levetiracetam, seguido de la carbamacepina y el ácido valproico. En monoterapia, el más frecuente fue la carbamacepina, con mayor proporción de control completo. Conclusiones. La epilepsia en la esclerosis tuberosa es relativamente benigna, y se consigue un aceptable control en la mayoría de casos con un número de antiepilépticos acorde con lo aconsejado en las guías de tratamiento. Se observa estabilidad de lesiones, y no hay malignización en nuestra serie. El bajo número de la muestra limita el estudio, pero se observan proporciones similares de efectividad del tratamiento respecto a otra serie publicada (AU)

Introduction. Tuberous sclerosis is a genetic disease, the main manifestations of which are the formation of neuroectodermal tumours, which are very often associated to secondary epilepsy. Aim. To describe the epileptic profile, control, frequency of seizures and effectiveness of treatment in adult patients with tuberous sclerosis. Patients and methods. The study was descriptive and included adult patients (over 14 years of age) with a confirmed diagnosis of tuberous sclerosis. Both the frequency and type of seizures were analysed. A study was conducted to analyse and record the number of different antiepileptic drugs in each patient and the frequency of use of each active ingredient, and the control of seizures and the type of therapy were also included in another comparative study. Results. Of a total of 19 adults who were studied, 16 of them (84%) had epileptic seizures. Results showed that 44%, 25% and 31% of them presented full control of seizures, sporadic seizures and frequent seizures, respectively. A certain frequency of focal, general and both types of seizures existed in 38%, 6% and 25%, respectively. Likewise, 38%, 44% and 19% of them were under treatment with antiepileptic drugs in monotherapy, bitherapy and tritherapy, respectively. Overall, the most commonly consumed drug was levetiracetam, followed by carbamazepine and valproic acid. In monotherapy the most common was carbamazepine, with a higher proportion of full control. Conclusions. Epilepsy in tuberous sclerosis is relatively benign and an acceptable degree of control is achieved in most cases with a number of the antiepileptic drugs recommended in the treatment guidelines. In our series, we observed stability of involvement and there was no progression to a malignant status. The small number of individuals in the sample limits the study, but the proportions of treatment effectiveness are seen to be similar to those observed in another series published in the literature (AU)

[Control of epilepsy in adult patients with tuberous sclerosis]. / Control de la epilepsia en pacientes adultos con esclerosis tuberosa.

INTRODUCTION: Tuberous sclerosis is a genetic disease, the main manifestations of which are the formation of neuroectodermal tumours, which are very often associated to secondary epilepsy. AIM: To describe the epileptic profile, control, frequency of seizures and effectiveness of treatment in adult patients with tuberous sclerosis. PATIENTS AND METHODS: The study was descriptive and included adult patients (over 14 years of age) with a confirmed diagnosis of tuberous sclerosis. Both the frequency and type of seizures were analysed. A study was conducted to analyse and record the number of different antiepileptic drugs in each patient and the frequency of use of each active ingredient, and the control of seizures and the type of therapy were also included in another comparative study. RESULTS: Of a total of 19 adults who were studied, 16 of them (84%) had epileptic seizures. Results showed that 44%, 25% and 31% of them presented full control of seizures, sporadic seizures and frequent seizures, respectively. A certain frequency of focal, general and both types of seizures existed in 38%, 6% and 25%, respectively. Likewise, 38%, 44% and 19% of them were under treatment with antiepileptic drugs in monotherapy, bitherapy and tritherapy, respectively. Overall, the most commonly consumed drug was levetiracetam, followed by carbamazepine and valproic acid. In monotherapy the most common was carbamazepine, with a higher proportion of full control. CONCLUSIONS: Epilepsy in tuberous sclerosis is relatively benign and an acceptable degree of control is achieved in most cases with a number of the antiepileptic drugs recommended in the treatment guidelines. In our series, we observed stability of involvement and there was no progression to a malignant status. The small number of individuals in the sample limits the study, but the proportions of treatment effectiveness are seen to be similar to those observed in another series published in the literature.

TITLE: Control de la epilepsia en pacientes adultos con esclerosis tuberosa.Introduccion. La esclerosis tuberosa es una enfermedad genetica cuyas manifestaciones principales son la formacion de tumores neuroectodermicos, que asocia epilepsia secundaria muy frecuentemente. Objetivo. Describir el perfil epileptico, el control, la frecuencia de crisis y la efectividad del tratamiento en pacientes adultos con esclerosis tuberosa. Pacientes y metodos. Estudio descriptivo en el que se han incluido pacientes adultos (mayores de 14 anos) con diagnostico confirmado de esclerosis tuberosa. Se ha analizado la frecuencia y tipos de crisis. Se ha realizado un estudio y contabilizacion de los diferentes farmacos antiepilepticos en cada paciente, la frecuencia de uso de cada principio activo y un estudio comparativo entre control de crisis y tipo de terapia. Resultados. De 19 adultos estudiados, tuvieron crisis epilepticas 16 (84%). Presentaron control de crisis completo, crisis esporadicas y crisis frecuentes el 44%, 25% y 31%, respectivamente. Hubo frecuencia de crisis focales, generalizadas y ambas en el 38%, 6% y 25%, respectivamente. Estaban en tratamiento con farmacos antiepilepticos en monoterapia, biterapia y triterapia el 38%, 44% y 19%, respectivamente. El mas consumido globalmente fue el levetiracetam, seguido de la carbamacepina y el acido valproico. En monoterapia, el mas frecuente fue la carbamacepina, con mayor proporcion de control completo. Conclusiones. La epilepsia en la esclerosis tuberosa es relativamente benigna, y se consigue un aceptable control en la mayoria de casos con un numero de antiepilepticos acorde con lo aconsejado en las guias de tratamiento. Se observa estabilidad de lesiones, y no hay malignizacion en nuestra serie. El bajo numero de la muestra limita el estudio, pero se observan proporciones similares de efectividad del tratamiento respecto a otra serie publicada.

[Healthcare management of an epilepsy clinic: factors involved in the demand for health care and clinical situation of patients]. / Gestion sanitaria de una consulta de epilepsia: factores implicados en la demanda asistencial y situacion clinica de los pacientes.

INTRODUCTION: Epilepsy is a chronic illness that requires a long-term periodic follow-up of the patient and this means that as time goes by the number of patients attended increases, with the ensuing added cost for the healthcare system. AIM: To determine the factors involved in the time until an epileptic patient's next visit. PATIENTS AND METHODS: Our sample consisted of a selection of patients who visited the epilepsy clinic at our hospital consecutively during one year. Their clinical situation and relationship with the medical advice they were given, together with the factors involved in the time elapsed until the next visit, were analysed by means of predictive econometric models. RESULTS: There is a clear association between the patient's clinical situation and the modification of the treatment proposed by the neurologist in the previous visit. The factors involved in the time until the next visit were the frequency of seizures, adverse side effects from medicines -above all those that affect cognition- and the medical advice given to the patient. Polytherapy, psychoaffective disorders or the patient's social situation were not found to be significant. CONCLUSIONS: Follow-up visits in a specific epilepsy clinic improves the patient's situation. This is the first analysis of the demand for healthcare in patients with epilepsy conducted by means of econometric methods and from a mixed physician-patient perspective. Since the factors that determine the time until the next visit can be modified, the number of visits per year could be reduced, thus improving patients' clinical situation. We suggest a greater amount of time should be spent per visit so as to be able to have a bearing on it and thereby cut costs in the long term.

TITLE: Gestion sanitaria de una consulta de epilepsia: factores implicados en la demanda asistencial y situacion clinica de los pacientes.Introduccion. La epilepsia es una enfermedad cronica que implica un seguimiento periodico del paciente a largo plazo, lo que supone un aumento del numero de pacientes visitados con el tiempo y, por tanto, un coste al sistema sanitario. Objetivo. Determinar los factores implicados en el tiempo para la siguiente visita de un paciente epileptico. Pacientes y metodos. Seleccion de pacientes durante un ano que acuden consecutivamente a consulta de epilepsia de nuestro hospital. Se analiza su situacion clinica y relacion con el consejo medico dado, y los factores implicados en el tiempo transcurrido hasta la siguiente visita mediante modelos econometricos predictivos. Resultados. Existe una clara asociacion entre la situacion clinica del paciente y la modificacion del tratamiento propuesta por el neurologo en la visita anterior. Los factores implicados en el tiempo hasta la siguiente visita fueron frecuencia de crisis, efectos adversos medicamentosos, sobre todo los que afectan a la cognicion, y consejo medico al paciente. No resultaron significativos la politerapia, los trastornos psicoafectivos ni la situacion social del paciente. Conclusiones. El seguimiento en una consulta especifica de epilepsia mejora la situacion del paciente. Se trata del primer analisis de demanda asistencial en pacientes con epilepsia realizado mediante metodos econometricos y desde una perspectiva mixta medico-paciente. Dado que los factores que determinan el tiempo para la siguiente visita son modificables, podria disminuir el numero de visitas al ano, mejorando la situacion clinica de los pacientes. Proponemos una mayor duracion por visita para poder incidir en ello y reducir costes a largo plazo.

Gestión sanitaria de una consulta de epilepsia: factores implicados en la demanda asistencial y situación clínica de los pacientes / Healthcare management of an epilepsy clinic: factors involved in the demand for health care and clinical

Introducción. La epilepsia es una enfermedad crónica que implica un seguimiento periódico del paciente a largo plazo, lo que supone un aumento del número de pacientes visitados con el tiempo y, por tanto, un coste al sistema sanitario. Objetivo. Determinar los factores implicados en el tiempo para la siguiente visita de un paciente epiléptico. Pacientes y métodos. Selección de pacientes durante un año que acuden consecutivamente a consulta de epilepsia de nuestro hospital. Se analiza su situación clínica y relación con el consejo médico dado, y los factores implicados en el tiempo transcurrido hasta la siguiente visita mediante modelos econométricos predictivos. Resultados. Existe una clara asociación entre la situación clínica del paciente y la modificación del tratamiento propuesta por el neurólogo en la visita anterior. Los factores implicados en el tiempo hasta la siguiente visita fueron frecuencia de crisis, efectos adversos medicamentosos, sobre todo los que afectan a la cognición, y consejo médico al paciente. No resultaron significativos la politerapia, los trastornos psicoafectivos ni la situación social del paciente. Conclusiones. El seguimiento en una consulta específica de epilepsia mejora la situación del paciente. Se trata del primer análisis de demanda asistencial en pacientes con epilepsia realizado mediante métodos econométricos y desde una perspectiva mixta médico-paciente. Dado que los factores que determinan el tiempo para la siguiente visita son modificables, podría disminuir el número de visitas al año, mejorando la situación clínica de los pacientes. Proponemos una mayor duración por visita para poder incidir en ello y reducir costes a largo plazo (AU)

Introduction. Epilepsy is a chronic illness that requires a long-term periodic follow-up of the patient and this means that as time goes by the number of patients attended increases, with the ensuing added cost for the healthcare system. Aim. To determine the factors involved in the time until an epileptic patient’s next visit. Patients and methods. Our sample consisted of a selection of patients who visited the epilepsy clinic at our hospital consecutively during one year. Their clinical situation and relationship with the medical advice they were given, together with the factors involved in the time elapsed until the next visit, were analysed by means of predictive econometric models. Results. There is a clear association between the patient’s clinical situation and the modification of the treatment proposed by the neurologist in the previous visit. The factors involved in the time until the next visit were the frequency of seizures, adverse side effects from medicines –above all those that affect cognition– and the medical advice given to the patient.Polytherapy, psychoaffective disorders or the patient’s social situation were not found to be significant. Conclusions. Follow-up visits in a specific epilepsy clinic improves the patient’s situation. This is the first analysis of the demand for healthcare in patients with epilepsy conducted by means of econometric methods and from a mixed physicianpatient perspective. Since the factors that determine the time until the next visit can be modified, the number of visits per year could be reduced, thus improving patients’ clinical situation. We suggest a greater amount of time should be spent per visit so as to be able to have a bearing on it and thereby cut costs in the long term (AU)