Epilepsia como una enfermedad de redes neuronales. Un punto de vista neurofisiológico / Epilepsy as a disease affecting neural networks: A neurophysiological perspective

Introducción: La epilepsia es un conjunto de redes de estructuras cerebrales representadas bilateralmente, que están funcional y anatómicamente conectadas; en la epilepsia, la actividad de cualquier parte del cerebro afecta la actividad de las demás. Esto es relevante para el entendimiento de la fisiopatología, la etiología, el diagnóstico y la prognosis de esta enfermedad.ObjetivoRevisar el estado del arte en cuanto al entendimiento de la visión neurofisiológica de la epilepsia como una enfermedad de redes neuronales.ResultadosSe describen los principios básicos y avanzados de la epilepsia como enfermedad de redes neuronales usando distintos métodos clínicos y matemáticos con una visión neurofisiológica, indicando las limitaciones de estos hallazgos en el contexto clínico.ConclusionesLa epilepsia es una enfermedad de redes neuronales complejas cuyo entendimiento permitirá mejorar los tratamientos disponibles y la certeza pronostica. (AU)

Introduction: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease.ObjectiveIn this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks.ResultsWe describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context.ConclusionsEpilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence. (AU)

Epilepsy as a disease affecting neural networks: a neurophysiological perspective.

INTRODUCTION: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease. OBJECTIVES: In this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks. RESULTS: We describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context. CONCLUSIONS: Epilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence.

Epilepsy as a disease affecting neural networks: A neurophysiological perspective. / Epilepsia como una enfermedad de redes neuronales. Un punto de vista neurofisiológico.

INTRODUCTION: The brain is a series of networks of functionally and anatomically connected, bilaterally represented structures; in epilepsy, activity of any part of the brain affects activity in the other parts. This is relevant for understanding the pathophysiology, diagnosis, and prognosis of the disease. OBJECTIVE: In this study, we present a state-of-the-art review of the neurophysiological view of epilepsy as a disease affecting neural networks. RESULTS: We describe the basic and advanced principles of epilepsy as a disease affecting neural networks, based on the use of different clinical and mathematical techniques from a neurophysiological perspective, and signal the limitations of these findings in the clinical context. CONCLUSIONS: Epilepsy is a disease affecting complex neural networks. Understanding these will enable better management and prognostic confidence.

Choice of antiepileptic drugs affects the outcome in cancer patients with seizures

Background: Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based on the antiepileptic drug used. Method: This is a prospective comparative study that included adult cancer patients with and without seizures from May 2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups, and Kaplan-Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used to describe survival and compare groups. Results: A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%) who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11% had a primary brain tumor. No survival differences were noted among patients with brain metastases or primary tumor with or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2 or more. A better overall survival was identified for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015), levetiracetam (p = 0.03), and valproic acid (p = 0.009). Conclusions: Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. However, patients with seizures not treated with antiepileptics exhibit worse overall survival

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[TK2 mutations and late onset myopathy: first description in a Mexican patient]. / Mutacion del gen TK2 y miopatia de inicio tardio: descripcion del primer caso mexicano.

TITLE: Mutacion del gen TK2 y miopatia de inicio tardio: descripcion del primer caso mexicano.

Choice of antiepileptic drugs affects the outcome in cancer patients with seizures.

BACKGROUND: Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based on the antiepileptic drug used. METHOD: This is a prospective comparative study that included adult cancer patients with and without seizures from May 2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups, and Kaplan-Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used to describe survival and compare groups. RESULTS: A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%) who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11% had a primary brain tumor. No survival differences were noted among patients with brain metastases or primary tumor with or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2 or more. A better overall survival was identified for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015), levetiracetam (p = 0.03), and valproic acid (p = 0.009). CONCLUSIONS: Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. However, patients with seizures not treated with antiepileptics exhibit worse overall survival.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study).

BACKGROUND AND PURPOSE: Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors. MATERIALS AND METHODS: This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included 279 patients. Both contrast agents (dose = 0.1 mmol/kg of body weight) were assessed with 2 identical MRIs at a time interval of 2-14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from "poor" to "excellent." Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site. RESULTS: For all 3 readers, images of most patients (>90%) were scored good or excellent for overall lesion visualization and characterization with either contrast agent; and the noninferiority of gadoterate meglumine versus gadobutrol was statistically demonstrated. No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentage enhancement being higher with gadobutrol (P < .001). Diagnostic confidence was high/excellent for all readers in >81% of the patients with both contrast agents. Similar percentages of patients with adverse events related to the contrast agents were observed with gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain. CONCLUSIONS: The noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors was demonstrated.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Seguridad del tratamiento antibiótico intravenoso domiciliario en pacientes adultos con fibrosis quística / Safety of home intravenous antibiotic treatment in adult patients with cystic fibrosis

Objetivo: Estudio descriptivo en el que se valoran los ciclos de tratamiento antibiótico domiciliario (TAIVD) que se han originado en una Unidad de FQ de adultos de 55 pacientes en un periodo de 5 años. Se analizaron las características de los pacientes, tipo de antibioterapia, acceso venoso utilizado, así como los dispositivos de administración, complicaciones surgidas y resolución de las mismas. Pacientes y métodos: Se incluyeron en el estudio los pacientes con FQ que recibieron TAIVD a lo largo del periodo enero 2002-diciembre 2006. Se recogieron las siguientes variables de los enfermos: edad, sexo, colonización bacteriana dela vía aérea y función pulmonar en fase estable. Resultados: 29 enfermos: 14 varones y 15 mujeres. Recibieron un total de 98 ciclos de antibioterapia intravenosa. La edad media fue de 25,31 (6,83) años. El 62% estaban colonizados por Pseudomonas aeruginosa. Los antibióticos más utilizados fueron ceftazidima y tobramicina. Los pacientes permanecieron una media de 3,62 (4,13) días ingresados en el hospital y 12,27 (4,16) en domicilio. En todos los casos se utilizó la vía periférica, salvo en 3 ciclos en que se usó catéter central de inserción periférica para la administración de los antibióticos. En el 37% de los casos se perdió el acceso venoso y en el 19,2% se produjo flebitis. La canalización de la nueva vía periférica se realizó en el 60,4% por la enfermera de la Unidad de FQ correspondiente, en un 23,25% por el hospital más cercano y en un 12,6% por el Centro de Salud. En 3 casos se presentaron reacciones cutáneas y en 4, alteraciones gastrointestinales secundarias al antibiótico. Conclusiones: La TAIVD es una modalidad terapéutica que, ajustándose a unos criterios de inclusión y exclusión predeterminados, presenta escasas complicaciones y permite reducir el número de estancias hospitalarias. Previsiblemente el uso de la TAIVD se incremente en los próximos años debido a la mayor expectativa de vida de estos enfermos y a que la terapia domiciliaria es la elegida por la población adulta con FQ (AU)

Objectives: A descriptive study of the home intravenous antibiotic treatment (HIVAT) course in CF Units of fifty five patients in period of six years. Different patient features were recorded, antibiotherapy, intravenous access, complications and their resolutions. We accessed the improvement of the pulmonary function, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) at the end of the treatment. Patients and Methods: For a five years period (January 2002-December 2006) the patients with CF who received HIVAT and fulfilled the previously fixed criteria were included. The next clinic variables were collected: age, sex, bacterial colonization of respiratory tree, pancreatic function and pulmonary function in steady phase. Results: 29 patients, 14 male and 15 female, were given 98 courses of HIAT. Mean age was 25.31 (6.83) years. 62% of the patients were colonized by Pseudomonas aeruginosa. The most frequently used antibiotics were ceftazidime and tobramycin. Courses of treatment lasted a mean of 3,62 (4,13) days inpatient and 12.27 (4.16) at home. The most of the course were used the intravenous cannula, but in three courses used insertion of peripheral central catheter. The intravenous access was replaced, in the 60.4% of the cases, by the nurse of the CF Unit, in the 23,25% in the emergency room of the nearest hospital and in 12,6% in primary care centre. Three occasions skin reactions were reported and four cases gastrointestinal disorders secondary to antibiotic. The parameters of pulmonary function improved significatively after HIVAT. Conclusions: The HIVAT is a therapeutic option that, following predetermined inclusion criteria, has a low complication rate and permit reduction hospitalization. Probably, HIVAT will be an increasing therapeutic option due to the rise of life expectancy and to that the domiciliary therapy is the chosen one by the adult population with CF (AU)