Advances in epilepsy: new perspectives on new-onset epilepsy, comorbidities, and pharmacotherapy

The purpose of this brief article is to review old concepts of the significance of acute symptomatic seizures, the impact of psychiatric comorbidities on the response of pharmacologic and surgical treatments of the seizure disorder, and the importance of factoring comorbid medical comorbidities into the choice of antiepileptic drugs (AEDs). In addition, this article provides an update on the latest data on the teratogenic effects of AEDs and reviews the most relevant results of a recent practice guideline on pregnancy issues in women with epilepsy. The article closes with a review of the latest advances in the therapeutic effects of first- and second-generation AEDs

Mood disorder and epilepsy: a neurobiologic perspective of their relationship

Mood disorders are the most frequent psychiatric comorbidity in epilepsy, and in particular in temporal lobe epilepsy. For a long time, depressive disorders were considered to be the expression of a reactive process to the obstacles of a life with epilepsy Data obtained in the last two decades, however, have demonstrated biochemical, neuropathoiogical, and neurophysioiogic changes mediating the development of mood disorders, which in fact can be tested in animal models. Furthermore, there is also evidence that mood disorders and epilepsy have a complex relationship which is bidirectional; that is, not only are patients with epilepsy at greater risk of developing depression, but patients with depression have a higher risk of developing epilepsy. Such a relationship can only be explained by the existence of common pathogenic mechanisms that are operant in both conditions. These include changes in neurotransmitters, such as serotonin, norepinephrine, glutamate, and γ-aminobutyric acid. Such a bidirectional relationship also appears to have important clinical consequences. Indeed, patients with a history of mood disorders are twice as likely to develop pharmacoresistant epilepsy as those without such a history. These data are reviewed in this article

Random-Field Blume-Capel Model: Mean-Field Theory

The global phase diagram of the Blume-Capel model in a random field obeying the bimodal symmetric distribution is determined by using the mean-field method. The phase diagram includes an isolated ordered critical end point and two lines of tricritical points. A new phase emerges for strong enough random fields: the ferromagnetic-nonmagnetic phase. It is argued that such a phase occurs in three dimensions

Psychiatric Comorbidities in People With Epilepsy.

Purpose of Review: To review the latest evidence concerning the epidemiology, clinical implications, and management of psychiatric disorders in epilepsy. Recent Findings: People with epilepsy have a 2-5 times increased risk of developing any psychiatric disorder, and 1 in 3 patients with epilepsy have a lifetime psychiatric diagnosis. Psychiatric comorbidities represent a poor prognostic marker as they have been associated with a poor response to treatment (drugs and surgery), increased morbidity, and mortality. Validated screening instruments are available for mood and anxiety disorders in adults as well as attention-deficit hyperactivity disorder in children with epilepsy. Summary: All patients with epilepsy should be routinely screened for psychiatric disorder at the onset and at least once a year. Patients with epilepsy and their relatives should be informed of the risk of mental health problems and the implications

Sculpting ion channel functional expression with engineered ubiquitin ligases

The functional repertoire of surface ion channels is sustained by dynamic processes of trafficking, sorting, and degradation. Dysregulation of these processes underlies diverse ion channelopathies including cardiac arrhythmias and cystic fibrosis. Ubiquitination powerfully regulates multiple steps in the channel lifecycle, yet basic mechanistic understanding is confounded by promiscuity among E3 ligase/substrate interactions and ubiquitin code complexity. Here we targeted the catalytic domain of E3 ligase, CHIP, to YFP-tagged KCNQ1 ± KCNE1 subunits with a GFP-nanobody to selectively manipulate this channel complex in heterologous cells and adult rat cardiomyocytes. Engineered CHIP enhanced KCNQ1 ubiquitination, eliminated KCNQ1 surface-density, and abolished reconstituted K+ currents without affecting protein expression. A chemo-genetic variation enabling chemical control of ubiquitination revealed KCNQ1 surface-density declined with a ~ 3.5 hr t1/2 by impaired forward trafficking. The results illustrate utility of engineered E3 ligases to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve effective post-translational functional knockdown of ion channels

Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation

AbstractPurposeThe primary efficacy and safety measures from a trial of responsive neurostimulation for focal epilepsy were previously published. In this report, the findings from the same study are presented for quality of life, which was a supportive analysis, and for mood, which was assessed as a secondary safety endpoint.MethodsThe study was a multicenter randomized controlled double-blinded trial of responsive neurostimulation in 191 patients with medically resistant focal epilepsy. During a 4-month postimplant blinded period, patients were randomized to receive responsive stimulation or sham stimulation, after which all patients received responsive neurostimulation in open label to complete 2years. Quality of life (QOL) and mood surveys were administered during the baseline period, at the end of the blinded period, and at year 1 and year 2 of the open label period.ResultsThe treatment and sham groups did not differ at baseline. Compared with baseline, QOL improved in both groups at the end of the blinded period and also at 1year and 2years, when all patients were treated. At 2years, 44% of patients reported meaningful improvements in QOL, and 16% reported declines. There were no overall adverse changes in mood or in suicidality across the study. Findings were not related to changes in seizures and antiepileptic drugs, and patients with mesial temporal seizure onsets and those with neocortical seizure onsets both experienced improvements in QOL.ConclusionsTreatment with targeted responsive neurostimulation does not adversely affect QOL or mood and may be associated with improvements in QOL in patients, including those with seizures of either mesial temporal origin or neocortical origin

Is it possible to enhance immune response after vaccination? The role of a probiotic with a proven positive effect on all components of the immune system

Preventive vaccination is currently the most affordable and economical way to reduce morbidity and mortality from many infections, improve quality and human life expectancy with an almost ideal balance of benefits and risks among all medical procedures. The article deals with the reasons for variability of the immune response caused by vaccines, between individuals and between populations, which is of fundamental importance for human health. The authors have presented data indicating a key role of the gut microbiota in the control of the immune response to vaccination. Particular attention is paid to the microbial diversity in different loci of the body. The role of microorganisms in the proper functioning of the body and the formation of a number of pathological conditions is described. Most modern vaccines are live-attenuated, killed / inactivated or subunit (recombinant) vaccines, and they are designed for the parenteral route of administration. Most of these vaccines elicit a weak immune response, especially in the mucous membranes, due to the route of administration and are associated with weak cell-mediated immunity. Therefore, mechanisms that can enhance virus-specific vaccine immunity in infants and children are required, such as the use of more potent or selective immunity-enhancing adjuvants. Some probiotic strains may be considered as promising vaccine adjuvants. This article evaluates the recent clinical studies of probiotics used to enhance vaccine-specific immunity in adults and infants. The present-day knowledge on the role of the probiotic strain Lactobacillus rhamnosus GG with the aim of activating immunity after vaccination are presented

Infant colic: from theory to practice

Infant colic is one of the most common, yet least studied, functional disorders of the gastrointestinal tract. Until now, there is no certainty both in the understanding of the nature of this condition and in the approaches to its correction. At the same time, infant crying is of concern to parents, forcing them to seek professional help and incur considerable medical expenses and to resort, sometimes unreasonably, to dietary and medical corrections. This article provides information on the etiology, pathogenesis and management of infantile colic from an evidence-based perspective, based on a review of the current literature. Various preconditions for the occurrence and development of infantile colic are analysed in detail, none of which can affect all occurrences. Evidence for the proven efficacy of including Lactobacillus reuteri in the treatment of intestinal colic in infants is presented. Effects on the gastrointestinal tract microbiome can be of undeniable benefit. Lactobacillus reuteri is one of the most studied and scientifically documented probiotics. 203 completed clinical trials involving 17,200 participants, including 67 trials involving 8,200 participants between 0 and 3 years of age. Numerous placebo-controlled studies have shown that taking Lactobacillus reuteri DSM 17938 can significantly reduce crying time in infants with colic, and in these studies, rates of 50% or more reduction in crying time were 2.3 times higher compared to controls