Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Congenital myasthenic syndrome due to mutation in CHRNE gene with clinical worsening and thymic hyperplasia attributed to association with autoimmune-myasthenia gravis.

We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl-choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG.

Two-year follow-up with eslicarbazepine acetate: a consecutive, retrospective, observational study.

PURPOSE: Eslicarbazepine acetate (ESL) is a new generation voltage-gated sodium channel blocker. It has completed one phase II clinical trial and three phase III clinical trials, two of which with 1-year open label extensions. ESL was approved in 2009 by the European Medicines Agency as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. It is marketed in Portugal since April 1st 2010. Despite good safety and efficacy shown in clinical trials, little is known about its effectiveness in a clinical day-to-day setting. Our purpose was to assess the post-marketing experience with ESL in our centre, in terms of safety and efficacy profile, and ascertain whether the results were comparable to the published data. METHODS: This is a retrospective, consecutive, single-centre 2-year observational study. All the patients who initiated treatment with ESL between April 1st 2010 and October 31st 2011 at Hospital de Santo António were consecutively included. Data was collected on demographics, clinical features, adverse events and treatment response, using a standardized data form. Follow-up data was considered until October 31st 2013. Efficacy analysis was performed using an "intention to treat" approach. KEY FINDINGS: We included 152 patients, 74 (48.7%) female. Mean age was 38.5 years-old (sd=14.2). Eight patients were less than 18 years old. Mean epilepsy duration was 26.8 (sd=13.1) years and mean seizure frequency in the previous 3 months was 19.7 seizures per month. At baseline, about 57.9% of all patients were taking ≤2 concomitant AEDs. The total adverse rate was 42.1% (64/152), with 50.0% (32/64) leading to treatment discontinuation. The most frequent adverse events were dizziness and somnolence/slowness. Adverse events were higher in regimens including carbamazepine, and mean age was higher in the patients reporting adverse events. Retention rates as estimated by Kaplan-Meyer curves were 82.9%, 71.3%, 65.1% and 62.8%, respectively, at 6, 12, 18 and 24 months. Retention time was not influenced by gender, diagnosis, age or epilepsy duration. Fifty-six patients (36.8%) dropped out of treatment, 32 (57.1%) due to adverse events, 19 (33.9%) due to lack of efficacy and 5 (8.9%) for other reasons. At 6,12,18 and 24 months, the responder rates were 25.7%, 25.7%, 19.0% and 17.1%, respectively and favourable global clinical impression rates were 27.7%, 19.7%, 17.8% and 16.5%. SIGNIFICANCE: This is the first study reporting follow-up data for up to 2 years in patients treated with ESL in the setting of daily clinical practice. The retention rates in our study are sustained throughout the 2 years of follow-up, and at 6 and 12 months are globally comparable to those of phase III trials and open-label extensions. The adverse event rate is also comparable to previous studies, and no new safety issues attributable to ESL were found. Responder rates were lower than those of previous studies, even though efficacy results must be interpreted with caution given the different study design. Thus, ESL appears to be a clinically useful add-on AED, with good safety profile and high retention rates, even in a very refractory group of patients like the presented cohort.

Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies.

PURPOSE: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. METHODS: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. KEY FINDINGS: Seizure frequency was significantly reduced with ESL 800 mg (p < 0.0001) and 1,200 mg (p < 0.0001) compared to placebo. Median relative reduction in seizure frequency was, respectively, 35% and 39% (placebo 15%) and responder rate was 36% and 44% (placebo 22%). ESL was more efficacious than placebo regardless of gender, geographic region, epilepsy duration, age at time of diagnosis, seizure type, and number and type of concomitant antiepileptic drugs (AEDs). Incidence of adverse events (AEs) and AEs leading to discontinuation were dose dependent. AEs occurred mainly during the first weeks of treatment, with no difference between groups after 6 weeks. Most common AEs (>10% patients) were dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. SIGNIFICANCE: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs.