Emerging drugs for partial-onset epilepsy: a review of brivaracetam

There are more than 12 new antiepileptic drugs approved in the last 2 decades. Even with these newer agents, seizure remission is still unachievable in around 30% of patients with partial-onset seizures (POS). Brivaracetam (BRV) is chemically related to levetiracetam (LEV) and possesses a strong binding affinity for the synaptic vesicle protein 2A tenfold above that of LEV, and other possible modes of antiepileptic actions. BRV is now under Phase III development for POS, but data from one Phase III trial also suggested its potential efficacy for primary generalized seizures. The purpose of this review is to provide updated information on the mechanisms of action of the available antiepileptic drugs, with a focus on BRV to assess its pharmacology, pharmacokinetics, clinical efficacy, safety, and tolerability in patients with uncontrolled POS. To date, six Phase IIb and III clinical trials have been performed to investigate the efficacy, safety, and tolerability of BRV as an adjunctive treatment for patients with POS. Generally, BRV was well tolerated and did not show significant difference in safety profile, compared to placebo. The efficacy outcomes of BRV, although not consistent across trials, did indicate that BRV was a promising add-on therapy for patients with POS. In conclusion, the many favorable attributes of BRV, like its high oral efficacy, good tolerability, dosing regimen, and minimal drug interaction, make it a promising antiepileptic therapy for patients with uncontrolled partial-onset epilepsy.

Distribution entropy analysis of epileptic EEG signals

It is an open-ended challenge to accurately detect the epileptic seizures through electroencephalogram (EEG) signals. Recently published studies have made elaborate attempts to distinguish between the normal and epileptic EEG signals by advanced nonlinear entropy methods, such as the approximate entropy, sample entropy, fuzzy entropy, and permutation entropy, etc. Most recently, a novel distribution entropy (DistEn) has been reported to have superior performance compared with the conventional entropy methods for especially short length data. We thus aimed, in the present study, to show the potential of DistEn in the analysis of epileptic EEG signals. The publicly-accessible Bonn database which consisted of normal, interictal, and ictal EEG signals was used in this study. Three different measurement protocols were set for better understanding the performance of DistEn, which are: i) calculate the DistEn of a specific EEG signal using the full recording; ii) calculate the DistEn by averaging the results for all its possible non-overlapped 5 second segments; and iii) calculate it by averaging the DistEn values for all the possible non-overlapped segments of 1 second length, respectively. Results for all three protocols indicated a statistically significantly increased DistEn for the ictal class compared with both the normal and interictal classes. Besides, the results obtained under the third protocol, which only used very short segments (1 s) of EEG recordings showed a significantly (p <; 0.05) increased DistEn for the interictal class in compassion with the normal class, whereas both analyses using relatively long EEG signals failed in tracking this difference between them, which may be due to a nonstationarity effect on entropy algorithm. The capability of discriminating between the normal and interictal EEG signals is of great clinical relevance since it may provide helpful tools for the detection of a seizure onset. Therefore, our study suggests that the DistEn analysis of EEG signals is very promising for clinical and even portable EEG monitoring.

Classification of 5-S epileptic EEG recordings using distribution entropy and sample entropy

Epilepsy is an electrophysiological disorder of the brain, the hallmark of which is recurrent and unprovoked seizures. Electroencephalogram (EEG) measures electrical activity of the brain that is commonly applied as a non-invasive technique for seizure detection. Although a vast number of publications have been published on intelligent algorithms to classify interictal and ictal EEG, it remains an open question whether they can be detected using short-length EEG recordings. In this study, we proposed three protocols to select 5 s EEG segment for classifying interictal and ictal EEG from normal. We used the publicly-accessible Bonn database, which consists of normal, interical, and ictal EEG signals with a length of 4097 sampling points (23.6 s) per record. In this study, we selected three segments of 868 points (5 s) length from each recordings and evaluated results for each of them separately. The well-studied irregularity measure-sample entropy (SampEn)-and a more recently proposed complexity measure-distribution entropy (DistEn)-were used as classification features. A total of 20 combinations of input parameters m and τ for the calculation of SampEn and DistEn were selected for compatibility. Results showed that SampEn was undefined for half of the used combinations of input parameters and indicated a large intra-class variance. Moreover, DistEn performed robustly for short-length EEG data indicating relative independence from input parameters and small intra-class fluctuations. In addition, it showed acceptable performance for all three classification problems (interictal EEG from normal, ictal EEG from normal, and ictal EEG from interictal) compared to SampEn, which showed better results only for distinguishing normal EEG from interictal and ictal. Both SampEn and DistEn showed good reproducibility and consistency, as evidenced by the independence of results on analysing protocol.

The Photooxidation of Domoic Acid

Domoic acid (DA) is a naturally occurring cyanotoxin, which upon ingestion, is responsible for amnesic shellfish poisoning (ASP) in both humans and animals. Produced by the marine diatom, Pseudonitzschia, DA is accumulated by a number of marine organisms including shellfish, clams and mussels which upon consumption can lead to headaches, nausea and seizures. Possessing a variety of functional groups the structure of DA contains three carboxyl groups, a pyrrole ring and a potent conjugated diene region allowing for binding to glutamate receptors in the dorsal hippocampus of the brain causing the described detrimental effects. Although limitations have been placed regarding the amount of DA that may be contained in seafood no limitations have been placed on the amount present in drinking water. Natural degradation of the toxin may occur through reactive oxygen species such as the hydroxyl radical and singlet oxygen at the conjugated diene region. In this work the photooxidation of DA via singlet oxygen has been studied using sorbic acid as a model compound. The three major reaction pathways observed during the photooxdiation process for both acids include 2 + 4 cycloaddition to produce endoperoxides , 2 + 2 reaction to afford aldehydes and ketones or an ene reaction to generate hydroperoxides. Under similar reaction conditions for SA and DA, the endoperoxide has been seen to be the major product for photoxidation of SA while the hydroperoxide has been seen to be the dominant product during photooxidation of DA.

Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy

Because GABA (gamma-aminobutyric acid) receptor-mediated inhibition controls the excitability of principal neurons in the brain, deficits in GABAergic inhibition have long been favored to explain seizures. In an experimental model of temporal lobe epilepsy, we have identified a deficit of inhibition in presynaptic GABAergic terminals characterized by decreased GABA quantal activity associated with reduced synaptic vesicle density. This decrease in vesicle number primarily seems to affect the reserve pool, rather than the docked or the readily releasable pool.

2016 Eastern Equine Encephalitis Activity

Eastern equine encephalitis virus (EEEV) is transmitted to humans by the bite of an infected mosquito. Eastern equine encephalitis (EEE) is a rare illness in humans, and only a few cases are reported in the United States each year. Most cases occur in the Atlantic and Gulf Coast states. Most people infected with EEEV have no apparent illness. Severe cases of EEE (involving encephalitis, an inflammation of the brain) begin with the sudden onset of headache, high fever, chills, and vomiting. The illness may then progress into disorientation, seizures, or coma. EEE virus is one of the most severe mosquito transmitted diseases in the United States with approximately 33% mortality and significant brain damage in most survivors. There is no specific treatment for EEE; care is based on symptoms. You can reduce your risk of being infected with EEEV by using insect repellent, wearing protective clothing, and staying indoors while mosquitoes are most active.

Depresión en pacientes con epilepsia: Revisión sistemática de la literatura

Esta revisión sistemática de la literatura tuvo como objetivo investigar sobre la depresión en personas con epilepsia en la última década (2005-2015), enfocándose en identificar en el paciente con epilepsia: características sociodemográficas, prevalencia de la depresión, tipos de intervención para el manejo de la depresión, factores asociados con la aparición y el mantenimiento de la depresión y por último, identificar las tendencias en investigación en el estudio de la depresión en pacientes con epilepsia. Se revisaron 103 artículos publicados entre 2005 y 2015 en bases de datos especializadas. Los resultados revelaron que la prevalencia de depresión en pacientes con epilepsia es diversa y oscila en un rango amplio entre 3 y 70 %, por otro lado, que las principales características sociodemográficas asociadas a la depresión está el ser mujer, tener un estado civil soltero y tener una edad comprendida entre los 25 y los 45 años. A esto se añade, que los tratamientos conformados por terapia psicológica y fármacos, son la mejor opción para garantizar la eficacia en los resultados del manejo de la depresión en los pacientes con epilepsia. Con respecto a los factores asociados a la aparición de la depresión en pacientes con epilepsia, se identificaron causas tanto neurobiológicas como psicosociales, asimismo los factores principales asociados al mantenimiento fueron una percepción de baja calidad de vida y una baja auto-eficacia. Y finalmente los tipos de investigación más comunes son de tipo aplicado, de carácter descriptivo, transversales y de medición cuantitativa.

Uso de dexmedetomidina como tratamiento coadyuvante de síndrome de abstinencia alcohólica: revisión sistemática

El objetivo de este estudio es establecer si la dexmedetomidina (DEX) es segura y efectiva para el manejo coadyuvante de síndrome de abstinencia a alcohol (SAA) a través de la búsqueda de evidencia científica. Metodología: se realiza una revisión sistemática de literatura publicada y no publicada desde enero de 1989 hasta febrero 2016 en PubMed, Embase, Scopus, Bireme, Cochrane library y en otras bases de datos y portales. Los criterios de inclusión fueron ensayos clínicos aleatorizados y no aleatorizados, estudios cuasi-experimentales, estudios de cohorte, y estudios de casos y controles; que incluyeron pacientes mayores de 18 años hospitalizados con diagnóstico de SAA y donde se usó DEX como terapia coadyuvante. Resultados: 7 estudios, 477 pacientes, se incluyeron en el análisis final. Se encontraron dos ensayos clínicos aleatorizados, tres estudios de casos y controles y dos estudios de cohorte retrospectivo. Solo uno de los estudios fue doble ciego y utilizó placebo como comparador. Análisis y conclusiones: en los estudios experimentales se determinan que el uso de DEX como terapia coadyuvante en el manejo de SAA tiene significancia clínica y estadística para disminuir dosis de BZD en las primeras 24 horas de tratamiento; pero no demostraron tener otros beneficios clínicos. En los estudios no aleatorizados existe consenso que relaciona el uso de DEX con menores dosis de BZD de forma temprana. Recomendaciones: no se recomienda el uso de DEX en SAA de forma rutinaria. Se recomienda usar DEX solo en casos en el que exista evidencia fallo terapéutico a BZD.

Infección por virus sincitial respiratorio y su relación con valores de IGG en niños críticos

Antecedente: La infección por el virus sincitial respiratorio (VSR) representa una elevada morbimortalidad, y en algunos casos necesidad de manejo en unidades de cuidado intensivo pediátrico (UCIP). La respuesta inmunológica influye de manera directa en la expresión de la severidad y pronóstico de los pacientes con infección respiratoria. Metodología: Estudio de una cohorte retrospectiva de pacientes con infección respiratoria grave secundaria a VSR, sin historia de inmunodeficiencia, atendidos en la UCIP del Hospital Universitario Clínica San Rafael. Se realizó análisis descriptivoglobaly de acuerdo a la categorización de las prueba de IgG. Resultados: De 188 pacientes que ingresaron a la UCIP, 13% presentaron infección por VSR (24), con una edad promedio de 7,3 (DE=3,6) meses. Pertenecían al sexo masculino79,83%. Se encontró que 12,5% tenían un valor de IgGbajo para su edad, 58,33% tenían valores en límite inferior y el 29,17% dentro de rangos normales para su edad. En los pacientes con IgG baja, fue mayor la presentación de choque séptico que no responde a líquidos (100 vs 92 vs 86%), la mediana de días de ventilación mecánica fue mayor (8 vs 6 vs 5 respectivamente), así como la mortalidad (67 vs 7,1 vs 0%). Conclusión: Nuestra serie encontró que aquellos pacientes con niveles bajos o valores en el límite inferior de IgG sérica tuvieron mayor compromiso sistémico, mayor duración de ventilación mecánica y mayor mortalidad. Se necesitan estudios prospectivos que relaciones niveles bajos de IgG con severidad y pronostico en estos pacientes con infección grave por VSR.

Crisis afásica simulando un ataque cerebrovascular isquémico agudo en el Servicio de Neurología del Hospital de San José de Bogotá DC

Se ha demostrado que la afasia como fenómeno ictal o postictal, se observa en cerca del 17% de los pacientes. Los casos en que es el único síntoma ictal, como en el estado epiléptico afásico, podría presentar un reto diagnóstico, y dependen de la sospecha diagnóstica del clínico. Presentamos el caso de un adulto mayor, que llega a urgencias por una alteración del lenguaje. Fue enfocado como un ataque cerebrovascular isquémico, pero después de evaluar la imagen de resonancia magnética cerebral simple se solicitó videotelemetría, que mostró descargas epileptiformes lateralizadas en región temporal izquierda, por lo que el paciente fue manejado como un estatus de afasia, con mejoría.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.