Short and long term prediction of seizure freedom in drug-resistant focal epilepsy surgery.

BACKGROUND: The selection of candidates for drug-resistant focal epilepsy surgery is essential to achieve the best post-surgical outcomes. OBJECTIVE: To develop two prediction models for seizure freedom in the short and long-term follow-up and from them to create a risk calculator in order to individualize the selection of candidates for surgery and future therapies in each patients. METHODS: A sample of 64 consecutive patients who underwent epilepsy surgery at two Cuban tertiary health institutions between 2012 and 2020 constituted the basis for the prediction models. Two models were obtained through the novel methodology, based on biomarker selection reached by resampling methods, cross-validation and high-accuracy index measured through the area under the receiving operating curve (ROC) procedure. RESULTS: The first, to pre-operative model included five predictors: epilepsy type, seizures per month, ictal pattern, interictal EEG topography and normal or abnormal magnetic resonance imaging,. it's precision was 0.77 at one year, and with four years and more 0.63. The second model including variables from the trans-surgical and post-surgical stages: the interictal discharges in the post-surgical EEG, incomplete or complete resection of the epileptogenic zone, the surgical techniques employed and disappearance of the discharge in post-resection electrocorticography; the precision of this model was 0.82 at one year, and with four years and more 0.97. CONCLUSIONS: The introduction of trans-surgical and post-surgical variables increase the prediction of the pre-surgical model. A risk calculator was developed using these prediction models, which could be useful as an accurate tool to improve the prediction in epilepsy surgery.

Impacto psicosocial del desarrollo científico-técnico en el estudio de la epilepsia

Introducción: Se ha planteado que no existe otra enfermedad asociada a tantos problemas sociales como lo es la epilepsia. Objetivo: Describir el impacto social del desarrollo científico-técnico en el estudio de la epilepsia. Método: Se realizó una revisión narrativa a partir del estudio documental de varias fuentes bibliográficas encontradas en base de datos electrónicas. Los principales criterios de búsqueda fueron: artículos publicados en los últimos 10 años sobre impacto psicosocial del desarrollo científico-técnico en el estudio de la epilepsia. Desarrollo: El efecto sobrenatural atribuido a la epilepsia, con su consecuente repercusión social, es resultado de especulaciones provocadas por siglos de falsas creencias sobre esta enfermedad. El impacto social de la enfermedad es negativo, genera problemas financieros, de aislamiento, de exclusión social y discriminación. Se plantea que la epilepsia tiene gran influencia en todos los niveles de calidad de vida. Las anomalías detectadas por las novedosas técnicas de estudio por neuroimagen en la epilepsia se han relacionado con el deterioro cognitivo, refractariedad de la enfermedad y otros hallazgos que pueden estar relacionados indirectamente con las alteraciones psicosociales de los pacientes. Consideraciones finales: La epilepsia, además del daño orgánico, genera consecuencias psicosociales negativas que limitan el desempeño saludable de los enfermos. En los últimos años los adelantos científico-técnicos han limitado de forma parcial los efectos sociales negativos de la enfermedad con la incorporación de novedosas tecnologías para su estudio y tratamiento.

Introduction: Views has been expressed that there is no disease more linked with social problems than epilepsy. Objective: To describe the social impact of scientific and technological development on the study of epilepsy. Method: A narrative review was carried out supported on the documentary research of several bibliographic sources found in electronic databases. The main search criteria were as follow: articles published in the last 10 years, which had relation with aspects concerning the psychosocial impact of scientific and technological development on the study of epilepsy. Development: The supernatural effect attributes to epilepsy, including its social repercussions, is the result of centuries of speculative theories and false beliefs about this disease. Epilepsy has negative impact on social well-being, causing serious economic problems, isolation, social exclusion and discrimination. Epilepsy is described as a disease with a great influence on all levels of quality of life. The abnormalities detected using novel neuroimaging techniques referred to the presence of cognitive impairment, refractory period and other aspects which may be indirectly related to psychosocial alterations in patients. Final considerations: Epilepsy, in addition to its traumatic effects, has negative psychosocial consequences that affect the healthy performance of patients. In recent years, the scientific and technological advancements have partially limited the negative social effects causes by this disease with the use of new technologies for its study and treatment.

Introdução: Tem sido sugerido que não há outra doença associada a tantos problemas sociais quanto a epilepsia. Objetivo: Descrever o impacto social do desenvolvimento científico-técnico no estudo da epilepsia. Método: Realizou-se revisão narrativa a partir do estudo documental de diversas fontes bibliográficas encontradas em bases de dados eletrônicas. Os principais critérios de busca foram: artigos publicados nos últimos 10 anos sobre o impacto psicossocial do desenvolvimento científico-técnico no estudo da epilepsia. Desenvolvimento: O efeito sobrenatural atribuído à epilepsia, com sua consequente repercussão social, é fruto de especulações causadas por séculos de falsas crenças sobre essa doença. O impacto social da doença é negativo, gera problemas financeiros, isolamento, exclusão social e discriminação. Sugere-se que a epilepsia tenha grande influência em todos os níveis da qualidade de vida. As anormalidades detectadas pelas novas técnicas de estudo de neuroimagem na epilepsia têm sido relacionadas à deterioração cognitiva, refratariedade da doença e outros achados que podem estar indiretamente relacionados às alterações psicossociais dos pacientes. Considerações finais: A epilepsia, além dos danos orgânicos, gera consequências psicossociais negativas que limitam o desempenho saudável dos pacientes. Nos últimos anos, os avanços técnico-científicos limitaram parcialmente os efeitos sociais negativos da doença com a incorporação de novas tecnologias para seu estudo e tratamento.

Evolución clínica, cognitiva y calidad de vida posquirúrgica en un caso con síndrome de Lennox Gastaut

Introducción: El síndrome de Lennox Gastaut se considera una encefalopatía epiléptica. Las anomalías epileptiformes en este síndrome contribuyen a la discapacidad intelectual gradual, a las comorbilidades psiquiátricas y alteraciones conductuales. En la práctica clínica aparecen atipicidades del síndrome, con focalización funcional cuyo tratamiento constituye un desafío. Objetivo: Describir la evolución clínica, cognitiva y calidad de vida en un caso con síndrome de Lennox Gastaut antes, y después del tratamiento quirúrgico. Presentación del caso: Paciente masculino de 16 años con síndrome de Lennox Gastaut. Se revisó la historia clínica y se tomaron en consideración, los resultados del video-electroencefalograma, de la resonancia magnética nuclear y de la tomografía computarizada por emisión de fotón único. Se evaluó, además, el proceder quirúrgico, la evaluación clínica y neuropsicológica. Se realizó una descripción cualitativa de la evolución del paciente a los 6 meses y al año de la intervención quirúrgica. Conclusiones: el paciente con síndrome de Lennox Gastaut presentó una evolución favorable después del tratamiento quirúrgico, lo cual se reflejó en una disminución en la frecuencia de las crisis. mejoría cognitiva, conductual y mejor calidad de vida.

Introduction: Lennox Gastaut syndrome is considered an epileptic encephalopathy. Epileptiform abnormalities in this syndrome contribute to gradual intellectual disability, psychiatric comorbidities and behavioral disturbances. In clinical practice, atypicalities of the syndrome appear with functional focalization whose treatment constitutes a challenge. Objective: To describe the clinical and cognitive evolution and quality of life in a case with Lennox Gastaut syndrome before and after surgical treatment. Case presentation: A 16-year-old male patient with Lennox Gastaut syndrome. The clinical history was reviewed and the results of the video-electroencephalogram, nuclear magnetic resonance and single photon emission computed tomography were taken into consideration. The surgical procedure, clinical and neuropsychological evaluation were also evaluated. A qualitative description of the patient's evolution past 6 months and one year after surgery was prepared. Conclusions: the patient with Lennox Gastaut syndrome has a favorable evolution after surgical treatment, which is reflected in a decrease in seizure frequency, cognitive and behavioral improvement and better quality of life.

Conectividad funcional a partir de la perfusión cerebral en pacientes epilépticos y con enfermedad de Parkinson / Functional connectivity from cerebral perfusion in patients with epilepsy and Parkinson's disease

Introducción: La epilepsia y la enfermedad de Parkinson han sido descritos como trastornos de redes neurales. El estudio de la conectividad por modalidades moleculares puede ser más relevante fisiológicamente que los basados en señales hemodinámicas. Objetivo: Proponer una metodología para la descripción de patrones de conectividad funcional a partir de la perfusión cerebral por tomografía por emisión de fotón único. Métodos: La metodología incluye cuatro pasos principales: preprocesamiento espacial, corrección del volumen parcial, cálculo del índice de perfusión y obtención de la matriz de conectividad funcional mediante el coeficiente de correlación de Pearson. Se implementó en 25 pacientes con distintos trastornos neurológicos: 15 con epilepsia farmacorresistente y 10 con enfermedad de Parkinson. Resultados: Se encontraron diferencias significativas entre los índice de perfusión de varias regiones de los hemisferios ipsilateral y contralateral tanto en pacientes con epilepsia del lóbulo frontal como en pacientes con epilepsia del lóbulo temporal. Igual resultado se obtuvo en los pacientes con enfermedad de Parkinson con distintos estadios de la enfermedad. Para cada grupo se identificaron patrones de conectividad funcional que involucran a regiones relacionadas con la patología en estudio. Conclusiones: Con el desarrollo de esta metodología se ha demostrado que la tomografía por emisión de fotón único aporta información valiosa para estudiar la organización de las redes funcionales del cerebro. Futuras investigaciones con mayor número de pacientes contribuirían a hacer inferencias sobre los correlatos neurales de los distintos trastornos cerebrales(AU)

Introduction: Epilepsy and Parkinson's disease have been described as disorders of neural networks. The study of connectivity by molecular modalities may be more physiologically relevant than those based on hemodynamic signals. Aim: The aim of the present work is to propose a methodology for the description of functional connectivity patterns from brain perfusion by single photon emission tomography. Methods: The methodology includes four main steps: spatial preprocessing, partial volume correction, calculation of the perfusion index and obtaining the functional connectivity matrix using Pearson's correlation coefficient. It was implemented in 25 patients with different neurological disorders: 15 with drug-resistant epilepsy and 10 suffering Parkinson's disease. Results: Significant differences were found between the perfusion indexes of various regions of the ipsilateral and contralateral hemispheres in both patients with frontal lobe epilepsy and patients with temporal lobe epilepsy. The same result was obtained in Parkinson's disease patients with different stages of the disease. For each group, functional connectivity patterns involving regions related to the pathology under study were identified. Conclusions: With the development of this methodology, it has been demonstrated that single photon emission tomography provides valuable information to study the organization of functional brain networks. Future research with a larger number of patients would contribute to make inferences about the neural correlates of the different brain disorders(AU)

The Effect of Neuroepo on Cognition in Parkinson's Disease Patients Is Mediated by Electroencephalogram Source Activity.

We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson's disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG.

Clinical Phenotypes and Mortality Biomarkers: A Study Focused on COVID-19 Patients with Neurological Diseases in Intensive Care Units.

Purpose: To identify clinical phenotypes and biomarkers for best mortality prediction considering age, symptoms and comorbidities in COVID-19 patients with chronic neurological diseases in intensive care units (ICUs). Subjects and Methods: Data included 1252 COVID-19 patients admitted to ICUs in Cuba between January and August 2021. A k-means algorithm based on unsupervised learning was used to identify clinical patterns related to symptoms, comorbidities and age. The Stable Sparse Classifiers procedure (SSC) was employed for predicting mortality. The classification performance was assessed using the area under the receiver operating curve (AUC). Results: Six phenotypes using a modified v-fold cross validation for the k-means algorithm were identified: phenotype class 1, mean age 72.3 years (ys)-hypertension and coronary artery disease, alongside typical COVID-19 symptoms; class 2, mean age 63 ys-asthma, cough and fever; class 3, mean age 74.5 ys-hypertension, diabetes and cough; class 4, mean age 67.8 ys-hypertension and no symptoms; class 5, mean age 53 ys-cough and no comorbidities; class 6, mean age 60 ys-without symptoms or comorbidities. The chronic neurological disease (CND) percentage was distributed in the six phenotypes, predominantly in phenotypes of classes 3 (24.72%) and 4 (35,39%); χ² (5) 11.0129 p = 0.051134. The cerebrovascular disease was concentrated in classes 3 and 4; χ² (5) = 36.63, p = 0.000001. The mortality rate totaled 325 (25.79%), of which 56 (17.23%) had chronic neurological diseases. The highest in-hospital mortality rates were found in phenotypes 1 (37.22%) and 3 (33.98%). The SSC revealed that a neurological symptom (ageusia), together with two neurological diseases (cerebrovascular disease and Parkinson's disease), and in addition to ICU days, age and specific symptoms (fever, cough, dyspnea and chilliness) as well as particular comorbidities (hypertension, diabetes and asthma) indicated the best prediction performance (AUC = 0.67). Conclusions: The identification of clinical phenotypes and mortality biomarkers using practical variables and robust statistical methodologies make several noteworthy contributions to basic and experimental investigations for distinguishing the COVID-19 clinical spectrum and predicting mortality.

Epilepsia del lóbulo temporal farmacorresistente como resultado de un programa quirúrgico / Drug-resistant temporal lobe epilepsy as a result of a surgical program

Introducción: La epilepsia del lóbulo temporal es la forma más común de epilepsia focal en el adulto y la que mejor responde al tratamiento quirúrgico. Objetivo: Identificar la asociación entre variables prequirúrgicas, transquirúrgicas y posquirúrgicas y la evolución en pacientes con epilepsia temporal farmacorresistente sometidos a cirugía de epilepsia. Métodos: Se estudiaron para la cirugía 24 pacientes con epilepsia temporal farmacorresistente, en el Instituto de Neurología y Neurocirugía, entre el año 2012 y 2020. Se utilizó el test de Fisher para identificar la asociación entre variables. Se evaluó la escala de Engel al año de la cirugía y en el último seguimiento. Resultados: Se alcanzó libertad de crisis (Engel I) en el 66,7 por ciento de los casos, según último seguimiento, con un período ente 1 a 8 años. La resección completa de la zona epileptogénica y la ausencia de crisis en los primeros 6 meses de la cirugía estuvieron relacionadas con Engel I al año y al último seguimiento. De igual forma las estadísticas estuvieron relacionadas: la ausencia de crisis posoperatorias agudas con Engel I al año y menos de 10 crisis al mes previo a la cirugía, la desaparición luego de la resección, del patrón epileptiforme encontrado en la electrocorticografía preresección, con Engel I al último seguimiento. Conclusiones: La mayoría de los pacientes operados de epilepsia del lóbulo temporal farmacorresistente quedaron libres de crisis en el último seguimiento. La resección completa de la zona epileptogénica y la ausencia de crisis en los primeros 6 meses de la cirugía estuvo asociada a las estadísticas de los resultados posquirúrgicos(AU)

Introduction: Temporal lobe epilepsy is the most common form of focal epilepsy in adults and the one that best responds to surgical treatment. Objective: to identify the association between pre-surgical, intra-surgical and post-surgical variables and evolution in patients with drug-resistant temporal epilepsy undergoing epilepsy surgery. Methods: Twenty four (24) patients with drug-resistant temporal epilepsy were studied for surgery at the Institute of Neurology and Neurosurgery, from 2012 to 2020. Fisher's test was used to identify the association between variables. The Engel scale was evaluated one year after surgery and at the last follow-up. Results: Seizure freedom (Engel I) was achieved in 66.7 percent of the cases, according to the last follow-up, with a period between 1 and 8 years. The complete resection of the epileptogenic zone and the absence of seizures in the first 6 months after surgery were related to Engel I at one year and at the last follow-up. In the same way, the statistics were related the absence of acute postoperative crises with Engel I a year and less than 10 crises a month prior to surgery, the disappearance, after resection, of the epileptiform pattern found in the pre-resection electrocorticography, with Engel I at last follow-up. Conclusions: The majority of patients operated on for drug-resistant temporal lobe epilepsy were seizure-free at the last follow-up. The complete resection of the epileptogenic zone and the absence of crises in the first 6 months after surgery were associated with the statistics of the postoperative results(AU)

Sequential Semiology of Seizures and Brain Perfusion Patterns in Patients with Drug-Resistant Focal Epilepsies: A Perspective from Neural Networks.

Ictal semiology and brain single-photon emission computed tomography have been performed in approaching the epileptogenic zone in drug-resistant focal epilepsies. The authors aim to describe the brain structures involved in the ictal and interictal epileptogenic network from sequential semiology and brain perfusion quantitative patterns analysis. A sequential representation of seizures was performed (n = 15). A two-level analysis (individual and global) was carried out for the analysis of brain perfusion quantification and estimating network structures from the perfusion indexes. Most of the subjects started with focal seizures without impaired consciousness, followed by staring, automatisms, language impairments and evolution to a bilateral tonic-clonic seizure (temporal lobe and posterior quadrant epilepsy). Frontal lobe epilepsy seizures continued with upper limb clonus and evolution to bilateral tonic-clonic. The perfusion index of the epileptogenic zone ranged between 0.439-1.362 (mesial and lateral structures), 0.826-1.266 in dorsolateral frontal structures and 0.678-1.507 in the occipital gyrus. The interictal epileptogenic network proposed involved the brainstem and other subcortical structures. For the ictal state, it included the rectus gyrus, putamen and cuneus. The proposed methodology provides information about the brain structures in the neural networks in patients with drug-resistant focal epilepsies.

Harmonized-Multinational qEEG norms (HarMNqEEG).

This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.

Surgical Outcome in Extratemporal Epilepsies Based on Multimodal Pre-Surgical Evaluation and Sequential Intraoperative Electrocorticography.

OBJECTIVE: to present the postsurgical outcome of extratemporal epilepsy (ExTLE) patients submitted to preoperative multimodal evaluation and intraoperative sequential electrocorticography (ECoG). SUBJECTS AND METHODS: thirty-four pharmaco-resistant patients with lesional and non-lesional ExTLE underwent comprehensive pre-surgical evaluation including multimodal neuroimaging such as ictal and interictal perfusion single photon emission computed tomography (SPECT) scans, subtraction of ictal and interictal SPECT co-registered with magnetic resonance imaging (SISCOM) and electroencephalography (EEG) source imaging (ESI) of ictal epileptic activity. Surgical procedures were tailored by sequential intraoperative ECoG, and absolute spike frequency (ASF) was calculated in the pre- and post-resection ECoG. Postoperative clinical outcome assessment for each patient was carried out one year after surgery using Engel scores. RESULTS: frontal and occipital resection were the most common surgical techniques applied. In addition, surgical resection encroaching upon eloquent cortex was accomplished in 41% of the ExTLE patients. Pre-surgical magnetic resonance imaging (MRI) did not indicate a distinct lesion in 47% of the cases. In the latter number of subjects, SISCOM and ESI of ictal epileptic activity made it possible to estimate the epileptogenic zone. After one- year follow up, 55.8% of the patients was categorized as Engel class I-II. In this study, there was no difference in the clinical outcome between lesional and non lesional ExTLE patients. About 43.7% of patients without lesion were also seizure- free, p = 0.15 (Fischer exact test). Patients with satisfactory seizure outcome showed lower absolute spike frequency in the pre-resection intraoperative ECoG than those with unsatisfactory seizure outcome, (Mann- Whitney U test, p = 0.005). CONCLUSIONS: this study has shown that multimodal pre-surgical evaluation based, particularly, on data from SISCOM and ESI alongside sequential intraoperative ECoG, allow seizure control to be achieved in patients with pharmacoresistant ExTLE epilepsy.

Prevención de la muerte súbita en la epilepsia fármaco resistente: investigaciones de enfermería / Prevention of sudden death in drug-resistant epilepsy: nursing research

Introducción: Una muerte súbita en epilepsia (SUDEP) ocurre cada diez minutos en todo el mundo. El 30 por ciento de los pacientes epilépticos padecen de epilepsia fármaco resistente (EFR), no logran el control de sus crisis y esto aumenta el riesgo de SUDEP. Muchos aún desconocen los factores de riesgo SUDEP y cómo prevenirlos. Los tratamientos para evitarla aún son insuficientes. Las investigaciones enfermeras aportan resultados positivos en el manejo de la enfermedad. Objetivo: Revisar el estado sobre mortalidad, autogestión de epilepsia e investigaciones enfermeras para prevenir la SUDEP en adolescentes y adultos con EFR. Material y Métodos: Revisión sistemática y búsqueda bibliográfica en las bases de datos PubMed SciELO, SCOPUS, ElSEVIER, MEDES, Organización Panamericana de la Salud (OPS), INFOMED y Google académico. Los criterios de selección: trabajos de la última década en adolescentes y adultos publicados en Cuba y el mundo, enfatizando en las investigaciones enfermeras. Búsqueda de palabras claves en español e inglés, sin restricciones de idioma. Desarrollo: Entre los tratamientos para evitar la SUDEP, destacan los dispositivos de detección de crisis y programas de ayuda online, pero aún son necesarias nuevas opciones. En los factores de riesgo, destacan aquellos relacionados con el sueño. Otros factores de riesgo SUDEP pudieran ser modificables con programas educativos. A pesar de que aún se debaten las formas más adecuadas de ofrecer información sobre SUDEP, los programas educativos enfermeros han evidenciado mayor autogestión, conocimiento de la enfermedad y apego al tratamiento. Conclusiones: El enfermero es el potencial humano ideal, para implementar acciones de autocuidado en las personas con EFR, y empoderarlas con habilidades para el manejo de su enfermedad y prevención de SUDEP(AU)

Introduction: A sudden death in epilepsy (SUDEP) occurs every ten minutes worldwide. Also, 30 percent of epileptic patients who suffer from drug-resistant epilepsy (DRE) fail to control their seizures, so the risk of SUDEP increases. Many epileptic patients are unaware of the risk factors for SUDEP and the ways to prevent it. Treatments to avoid SUDEP are still insufficient. Nursing research provide positive results in the management of the disease. Objective: To review the mortality status, self-management of epilepsy and nursing research to prevent SUDEP in adolescents and adults with DRE. Material and Methods: A systematic review and bibliographic search was carried out in the PubMed SciELO, SCOPUS, ELSEVIER, MEDES, Pan American Health Organization (PAHO), INFOMED and Google Scholar databases. Selection criteria included studies on nursing research conducted in adolescents and adults during the last decade that have been published in Cuba and other countries of the world. Keywords in Spanish and English without language restrictions were used to carry out the search. Development: Crisis detection devices and online help programs stand out among the treatments to avoid SUDEP, but new options are still necessary. Among the risk factors for SUDEP, those related to sleep are highlighted. Other risk factors for SUDEP could be modified with educational programs. Despite the most appropriate ways of offering information about SUDEP are still debated, nursing educational programs have shown greater self-management, knowledge of the disease, and adherence to treatment. Conclusions: The Nurse is the ideal human potential to implement self-care actions in people with EFR. These actions aim to learn new skills for managing their disease and preventing SUDEP(AU)

Functional Connectivity Derived From Electroencephalogram in Pharmacoresistant Epileptic Encephalopathy Using Cannabidiol as Adjunctive Antiepileptic Therapy.

To explore brain function using functional connectivity and network topology derived from electroencephalogram (EEG) in patients with pharmacoresistant epileptic encephalopathy with cannabidiol as adjunctive antiepileptic treatment. Sixteen epileptic patients participated in the study, six of whom had epileptic encephalopathy with a stable dose of cannabidiol Epidiolex (CBD) as adjunctive therapy. Functional connectivity derived from EEG was analyzed based on the synchronization likelihood (SL). The analysis also included reconstructing graph-theoretic measures from the synchronization matrix. Comparison of functional connectivity data between each pathological group with the control group was carried out using a nonparametric permutation test applied to SL values between pairs of electrodes for each frequency band. To compare the association patterns between graph-theoretical properties of each pathological group with the control group, Z Crawford was calculated as a measure of distance. There were differences between pairs of electrodes in all frequency bands evaluated in encephalopathy epileptic patients with CBD adjunctive therapy compared with the control (p < 0.05, permutation test). In the epileptic encephalopathy group without CBD therapy, the SL values were higher than in the control group for the beta, theta, and delta EEG frequency bands, and lower for the alpha frequency band. Interestingly, patients who had CBD as adjunctive therapy demonstrated greater synchronization for all frequency bands, showing less spatial distribution for alpha frequency compared with the control. When comparing both epileptic groups, those patients who had adjunctive CBD treatment also showed increased synchronization for all frequency bands. In epileptic encephalopathy with adjunctive CBD therapy, the pattern of differences for graph-theoretical measures according to Z Crawford indicated less segregation and greater integration suggesting a trend towards the random organization of the network principally for alpha and beta EEG bands. This exploratory study revealed a tendency to an overconnectivity with a random network topology mainly for fast EEG bands in epileptic encephalopathy patients using CBD adjunctive therapy. It can therefore be assumed that the CBD treatment could be related to inhibition of the transition of the interictal to ictal state and/or to the improvement of EEG organization and brain function.

Short-term Tolerance of Nasally-administered NeuroEPO in Patients with Parkinson Disease.

INTRODUCTION: No neuroprotective treatment has been able to successfully halt the progression of Parkinson disease or prevent development of associated complications. Recombinant erythropoetin (EPO), an erythropoiesis-stimulating agent originally indicated in anemia, produced and manufactured in Cuba (iorEPOCIM, CIMAB S.A, Havana, Cuba) has neuroprotective properties. NeuroEPO is a new nasal formulation of recombinant EPO with a low content of sialic acid and without hematopoietic effects. It has neuroprotective effects in animal models. OBJECTIVE: Evaluate short-term tolerance of intranasal NeuroEPO in patients with Parkinson disease. METHODS: As part of a monocentric randomized placebo-controlled double-blind study (registered at www.clinicaltrials.gov number NCT04110678), 26 patients with Parkinson disease (stages 1 and 2 on Hoehn & Yahr Scale), were randomly divided into two groups: NeuroEPO (n = 15) and placebo (n = 11), both treated intranasally either with the drug (1 mL, at a concentration of 1 mg/mL of NeuroEPO) or placebo once a week for 5 weeks. At each application, we recorded any adverse events and blood pressure. To assess potential hematopoietic effects of the drug, hematological and biochemical variables were evaluated one week before and one week after the intervention. RESULTS: There were no significant differences (p = 0.22) between the two groups in terms of frequency of adverse events (20.0% in NeuroEPO and 9.1% in placebo groups). Three patients in NeuroEPO presented nausea, and one vomited (possibly due to the patient's positioning during drug application). One patient in placebo group reported polyuria and nasal irritation. In both groups, the adverse events were mild, brief, required no treatment and did not present sequelae. CONCLUSIONS: Nasally administered NeuroEPO for five weeks in patients with Parkinson disease stages 1 and 2 on Hoehn & Yahr Scale is well tolerated.

Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson's Patients.

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson's Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs.

Cirugía de zona epileptogénica localizada en un área elocuente dellóbulo frontal en un adolescente con epilepsia / Epileptogenic zone surgery located in an eloquent area of the frontal lobe in an adolescent with epilepsy

Objetivo: Describir los resultados de la evaluación prequirúrgica, transquirúrgica y postquirúrgica, en un adolescente con epilepsia farmacorresistente con zona epileptogénica estimada en un área elocuente del lóbulo frontal izquierdo.Caso clínico: Paciente masculino, de 18 años, con epilepsia frontal izquierdafarmacorresistente desde los tres años, con una frecuencia de crisis de desconexión, atónicas y, en ocasiones, tónico clónico bilateral entre 30 y 40 diarias, previo a la cirugía. Laevaluación prequirúrgica identificó la zona de inicio ictal frontal izquierda, no lesional por imagen de resonancia magnética de 3 tesla. Se indicó tomografía computarizada por emisiónde fotón único interictal / ictal corregistrada con resonancia magnética, donde se identificó hiperperfusión frontal izquierda. Se realizó la cirugía con el uso de potenciales evocadossomatosensoriales para identificar el surco central, la estimulación cortical directa para mapear el área motora primaria, y la electrocorticografía transoperatoria para delimitar la zona de resección. Se empleó la técnica combinada desconectiva (callosotomía anterior) y resectiva del giro frontal superior y medio izquierdos, con modificación del patrón eléctrico en la electrocorticografía posterior a la cirugía. El resultado anatomopatológico fue displasia cortical focal tipo IA. En el seguimiento postquirúrgico, el paciente presenta solo entre 2-3 crisis semanales.Conclusiones: La cirugía de epilepsia extratemporal no lesional y con zona epileptogénica que incluye áreas elocuentes del lóbulo frontal es factible de realizar en nuestro país con mínima invasividad y buenos resultados(AU)

Objective: To describe the results of pre-surgical, trans-surgical and post-surgical assessment of an adolescent with drug-resistant epilepsy and an estimated epileptogenic zone in an eloquent area of the left frontal lobe.Clinical case: Male patient, 18 years old, who had drug-resistant left frontal epilepsy since the age of three. Before surgery, the patient suffered 30 and 40 daily disconnection episodes, atonic and, occasionally, daily bilateral clonic tonic. The pre-surgical evaluation identifiedthe left frontal, non-lesional ictal onset zone using 3-tesla magnetic resonance imaging. An interictal / ictal single photon emission computed tomography corrected with magnetic resonance imaging was indicated, which identified left frontal hyperperfusion. Surgery wasperformed using somatosensory-evoked potentials to identify the central sulcus, direct cortical stimulation to map the primary motor area, and intraoperative electrocorticography to delimit the resection area. Combined disconnective technique (anterior callosotomy) andresective technique of the left superior and middle left gyrus was used, modifying the electrical pattern in the electrocorticography after surgery. The pathological result was type IA focal cortical dysplasia. In the post-surgical follow-up, the patient only has 2-3 weekly crises.Conclusions: Surgery is feasible in a non-lesional extra-temporal epilepsy with an epileptogenic zone that includes eloquent frontal lobe areas in our country with minimal invasiveness and good results(AU)

Trastornos del sueño en pacientes con enfermedad de Parkinson / Sleep disorders in patients with Parkinson's disease

Objetivo: Evaluar la frecuencia de presentación de los trastornos del sueño según edad, sexo y tiempo de evolución.Métodos: Se realizó un estudio descriptivo de corte transversal por medio de una entrevista, examen clínico y estudio de polisomnografía a 77 pacientes con diagnóstico de enfermedadde Parkinson, remitidos al Centro Internacional de Restauración Neurológica, La Habana, Cuba, en el periodo comprendido entre septiembre de 2014 a enero de 2018. Se evaluóla edad, sexo y el tiempo de evolución de la enfermedad de Parkinson en función de los trastornos del sueño diagnosticados por polisomnografía. Se empleó la estadística descriptiva, así como el análisis no paramétrico (Kruskal-Wallis).Resultados: La evaluación mostró resultados dentro de parámetros normales en 6,49 Por ciento de los pacientes, trastorno del comportamiento del sueño de movimientos oculares rápidos en 29,87 Por ciento, insomnio en 29,87 Por ciento (principalmente, el tipo de mantenimiento del sueño),síndrome de apnea obstructiva del sueño en 25,97 Por ciento y el síndrome de piernas inquietas asociado con el movimiento periódico de las piernas durante el sueño en 7,79 Por ciento. Estos trastornos presentaron un comportamiento similar entre ambos sexos, así como una tendencia a empeorar con la edad y el tiempo de evolución.Conclusiones: Se detectó una alta prevalencia de trastornos del sueño en pacientes con enfermedad de Parkinson, los cuales no reflejan variaciones de acuerdo con el sexo; sin embargo, fueron más frecuentes en los pacientes de mayor edad o de mayor tiempo deevolución(AU)

Objective: To evaluate the frequency of sleep disorders occurrence according to age, sex and period of evolution.Methods: A descriptive cross-sectional study was conducted through interview, clinical examination and polysomnography study of 77 patients diagnosed with Parkinson's disease,these subjects were referred to the International Center for Neurological Restoration, Havana, Cuba, from September 2014 to January 2018. Age, sex, and evolution time of Parkinson's disease were evaluated based on sleep disorders diagnosed by polysomnography. Descriptive statistics were used, as well as non-parametric analysis (Kruskal-Wallis).Results: The evaluation showed results within normal parameters in 6.49 Per cent of the patients, rapid eye movement sleep behavior disorder in 29.87 Per cent, insomnia in 29.87 Per cent (mainly, type of sleep maintenance insomnia) , obstructive sleep apnea syndrome in 25.97 Per cent and restlesslegs syndrome associated with periodic movement of the legs during sleep in 7.79 Per cent. These disorders showed similar behavior in both sexes, as well as a tendency to worsen with ageand time of evolution.Conclusions: High prevalence of sleep disorders was detected in patients with Parkinson's disease, which do not reflect variations according to sex; however, they were more frequentin older patients or patients with a longer evolution period(AU)

Potencial P300 durante una tarea de atención sostenida en pacientes conenfermedad de Parkinson / P300 event-related potential during sustained attention in Parkinson's disease patients

Objetivo: Evaluar la relación entre el potencial relacionado a eventos P300 con significado atencional visual y los resultados de la evaluación neuropsicológica en pacientes conenfermedad de Parkinson en estadios II y III de Hoehn y Yahr.Métodos: Se realizó un estudio analítico transversal donde se evaluaron 57 pacientes con enfermedad de Parkinson idiopática, atendidos entre diciembre de 2017 y abril de 2018, en el Centro Internacional de Restauración Neurológica, de La Habana. Se realizó el registro de P300, durante la ejecución de una tarea de atención sostenida visual. Se midió latencia y amplitud de la P300, lo que se correlacionó (test de correlaciones de Spearman, p< 0,01)con las variables demográficas, variables de eficiencia en la tarea de atención sostenida y variables neuropsicológicas. Se compararon los resultados de los grupos II y III de Hoehn y Yahr con respecto a todas las variables estudiadas (test de la U de Mann Whitney, p< 0,05).Resultados: Se constató una significativa diferencia de latencia entre grupos del componente P300 en el electrodo Pz. Fue más prolongado en el grupo III de Hoehn y Yahr.Se evidenciaron en el grupo II correlaciones negativas entre la latencia de P300 y el test de batería de evaluación frontal, y positivas entre la latencia de P300 y la prueba de Stroop.Las correlaciones entre el test de ba(AU)

Objective: To evaluate the relationship between the P300 event-related potential with visual attention significance and the results of neuropsychological evaluation in patientswith Parkinson's disease in Hoehn and Yahr stages II and III.Methods: A cross-sectional analytical study was carried out evaluating 57 patients with idiopathic Parkinson's disease, who were treated from December 2017 to April 2018 at theInternational Center for Neurological Restoration, in Havana. P300 was recorded during the execution of a visual sustained attention task. The latency and amplitude of P300 weremeasured, which was correlated (Spearman's correlation test, p <0.01) with demographic variables, efficiency variables in the sustained attention task and neuropsychological variables. The results of Hoehn and Yahr groups II and III were compared with respect to all the variables studied (Mann Whitney U test, p <0.05).Results: Significant latency difference was found between groups of P300 component in Pz electrode. It was more prolonged in Hoehn and Yahr group III. Negative correlations were found in group II between P300 latency and the frontal evaluation battery test, andpositive correlations between P300 latency and Stroop test. The correlations between the frontal evaluation battery test and P300 amplitude were positive, and between Stroop test and P300 amplitude were negative. Similar results were evident in group III regarding P300 amplitude, which corresponded to worse performance in the neuropsychological evaluation.Conclusions: A close relationship between P300 event-related potential with visual attention significance and the results of the neuropsychological evaluation in Parkinson's disease patients, in Hoehn and Yahr stages II and III, was verified. P300 potential was an objective examination that reinforced the validity of the neuropsychological evaluationresults(AU)

Funcionamiento familiar y esfuerzo percibido por el cuidador primario de niños con enfermedades neurológicas / Family functioning and perceived effort by the primary caregiver of children with neurological diseases

RESUMEN Fundamento: Las investigaciones que intentan relacionar el funcionamiento familiar y el esfuerzo percibido por el cuidador primario de niños con enfermedades neurológicas, documentan resultados divergentes e insuficientes. Objetivo: identificar la relación entre el funcionamiento familiar y el esfuerzo percibido por el cuidador primario de niños con enfermedades neurológicas. Métodos: estudio de serie de casos, realizado en el Servicio de Neuropsicología, del Centro Internacional de Restauración Neurológica, en el segundo semestre de 2018. Los participantes fueron 12 cuidadores de niños entre uno y seis años de edad. Se aplicó entrevista estructurada, índice de esfuerzo del cuidador, escala de funcionamiento familiar/FF-SIL, inventario de características familiares de riesgo y análisis documental. Se utilizó estadística descriptiva, comparación de medias y correlación de Spearman. Resultados: el 92 % de los cuidadores no había recibido información de cómo cuidarse, ni de cómo cuidar a su hijo. El índice de esfuerzo del cuidador manifestó iguales proporciones para los niveles elevado y bajo (50 % respectivamente). Se observó relación entre edad de los cuidadores y edad de desarrollo de los niños y el funcionamiento familiar (r=0,71, r=0,67); así como entre el índice de esfuerzo del cuidador y el inventario de riesgos familiares (r=0,72). Conclusión: Los cuidadores primarios estudiados carecen de información de autocuidado y del cuidado de su hijo; una criticidad elevada y un índice de esfuerzo del cuidador heterogéneo, lo cual se relaciona con los riesgos familiares. La edad de los cuidadores y la edad de desarrollo de los niños influyen en el funcionamiento familiar.

ABSTRACT Foundation: Research that attempts to relate family functioning and the effort perceived by the primary caregiver of children with neurological diseases, documents divergent and insufficient results. Objective: to identify the relationship between family functioning and the effort perceived by the primary caregiver of children with neurological diseases. Methods: case series study, conducted at the Neuropsychology Service, of the International Center for Neurological Restoration, in the second half of 2018. The participants were 12 children caregivers between one and six years old. Structured interview, caregiver effort index, family functioning scale / FF-SIL, inventory of family risk characteristics and documentary analysis were applied. Descriptive statistics, comparison of means and Spearman correlation were used. Results: 92% of caregivers had not received information on how to take care of themselves, or how to care for their child. The caregiver effort index showed equal proportions for the high and low levels (50% respectively). The relationship between caregivers´ age, children´s development age and family functioning was observed (r = 0.71, r = 0.67); as well as between the caregiver's effort index and the family risk inventory (r = 0.72). Conclusion: The primary caregivers studied lack self-care information and care of their child; a high criticality and an effort index of the heterogeneous caregiver, which is related to family risks. The age of caregivers and the age of children´s development influence family functioning.

New Aspects of VEGF, GABA, and Glutamate Signaling in the Neocortex of Human Temporal Lobe Pharmacoresistant Epilepsy Revealed by RT-qPCR Arrays.

In the epilepsy spectrum, temporal lobe epilepsy (TLE) is the most common and devastating focal and symptomatic epilepsy form in adults, where more than 30% of patients develop pharmacoresistance. It is not fully understood how the gene expression contributes to establishing an epileptic phenotype. Cerebrovascular remodeling directed by VEGF (vascular endothelial growth factor) signaling might modulate the synaptic neurotransmission in the epileptic brain. To address this question, the gene expression was profiled in biopsies of the temporal cortex from diagnosed patients with pharmacoresistant TLE that underwent surgical resection to seizure control. One hundred sixty-eight genes related to VEGF signaling and GABA and glutamate neurotransmissions were evaluated. Genes related to downstream signaling -phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPK), and Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT) pathways- and neurotransmitters metabolism were evaluated too. Thirty-nine genes were upregulated. The genes encoding for G protein q polypeptide, serine racemase, gephyrin, and glutamate/cystine antiporter system xCT appeared as novel upregulated genes in the pharmacoresistant TLE. ClueGO, a Cytoscape plugin, was used to build a gene network associated using Gene Ontology (GO) terminology. Enrichment analysis by ClueGO retrieves that positive regulation of endothelial cell proliferation, nerve development, and neuronal apoptosis were over-represented categories. In conclusion, VEGF signaling is confirmed as a relevant mediator in the pharmacoresistant TLE. In addition, the enrichment analysis applied to differentially expressed genes suggests new pharmacological targets to be assessed in the treatment of pharmacoresistant TLE. Results make up an approximation to better understand the epileptic brain and complement the available data.

Vertical transmission of SARS-CoV-2. Impact on the nervous system. / Transmisión vertical del SARS-CoV-2. Impacto en el sistema nervioso.

Since the World Health Organization (WHO) announced the COVID-19 pandemic, SARS-CoV-2 infections have had a profound impact on public health. In this scenario an increasing number of women will be affected; equally, fetuses and newborns could be particularly vulnerable to the harmful effects of congenital or perinatally-acquired infections. In this study it is reviewed the available evidence on the potential intrauterine vertical SARS-CoV-2 transmission, after an exhaustive review of publications indexed until April 2020 in the United States' National Library of Medicine (PubMed/Medline). Starting from the analogies made with TORCH infections (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), and other coronaviruses, it is provided a pensive look about the potential impact of SARS-CoV-2 on the central nervous system (CNS). Lessons learned from the effects on CNS of other epidemics from TORCH viruses, as Zika virus in Brazil, and the analogy with the findings in animal models, pose the risk of congenital and perinatally-acquired infections, which are related to SARS-CoV-2. The effects of SARS-CoV-2 infection in the first trimester of pregnancy are unknown, and there are still many questions about its potential impact on CNS.

Desde que la Organización Mundial de la Salud (OMS) declaró la pandemia de COVID-19, las infecciones por SARS-CoV-2 han tenido un profundo impacto en la salud pública. En este escenario se afectará a un número creciente de mujeres embarazadas; asimismo, los fetos y los recién nacidos podrían ser especialmente vulnerables a las consecuencias dañinas de la infección adquirida de manera congénita o perinatal. En este trabajo se revisan las evidencias disponibles sobre la potencial transmisión vertical intrauterina de la infección por SARS-CoV-2, tras una revisión exhaustiva de las publicaciones indexadas hasta abril de 2020 en la Biblioteca Nacional de Medicina de los Estados Unidos (PubMed/Medline). Partiendo de las analogías con infecciones TORCH (Toxoplasma gondii, virus de la rubéola, citomegalovirus y virus del herpes) y otros coronavirus, se ofrece una mirada reflexiva sobre los efectos potenciales en el sistema nervioso central (SNC). Las lecciones aprendidas sobre los efectos en el SNC de otras epidemias por virus TORCH, como la del virus Zika en Brasil, y la analogía con los hallazgos en modelos animales, plantean el riesgo de infecciones congénitas y adquiridas perinatalmente, las cuales están relacionadas con el SARS-CoV-2. Se desconocen hoy las consecuencias de la infección por el SARS-CoV-2 en el primer trimestre del embarazo, y persisten muchas interrogantes sobre su impacto potencial en el SNC.