Chronic Brain Disease Research Articles

Toward the use of novel alternative methods in epilepsy modeling and drug discovery.

Epilepsy is a chronic brain disease and, considering the amount of people affected of all ages worldwide, one of the most common neurological disorders. Over 20 novel antiseizure medications (ASMs) have been released since 1993, yet despite substantial advancements in our understanding of the molecular mechanisms behind epileptogenesis, over one-third of patients continue to be resistant to available therapies. This is partially explained by the fact that the majority of existing medicines only address seizure suppression rather than underlying processes. Understanding the origin of this neurological illness requires conducting human neurological and genetic studies. However, the limitation of sample sizes, ethical concerns, and the requirement for appropriate controls (many patients have already had anti-epileptic medication exposure) in human clinical trials underscore the requirement for supplemental models. So far, mammalian models of epilepsy have helped to shed light on the underlying causes of the condition, but the high costs related to breeding of the animals, low throughput, and regulatory restrictions on their research limit their usefulness in drug screening. Here, we present an overview of the state of art in epilepsy modeling describing gold standard animal models used up to date and review the possible alternatives for this research field. Our focus will be mainly on ex vivo, in vitro, and in vivo larval zebrafish models contributing to the 3R in epilepsy modeling and drug screening. We provide a description of pharmacological and genetic methods currently available but also on the possibilities offered by the continued development in gene editing methodologies, especially CRISPR/Cas9-based, for high-throughput disease modeling and anti-epileptic drugs testing.

Clinical and economic implications of epilepsy management across treatment lines in Spain: a real-life database analysis

BackgroundEpilepsy is a chronic brain disease characterized by recurrent seizures. We investigated real-world management of epilepsy across treatment lines in Spain, including healthcare resource use (HRU) and associated costs.MethodsThis was a retrospective study of real-life data from epilepsy patients prescribed antiseizure medication (ASM) between January 2016 and December 2021. Patients were grouped according to their line of treatment (1st, 2nd, 3rd and 4th +) during the recruitment period. Demographic and clinical characteristics, comorbidities and concomitant medications were analyzed during the baseline period (6 months before starting treatment line); antiepileptic treatments, concomitant medications, HRU and associated costs were analyzed during follow-up.ResultsThe study included 5006 patients. Treatment duration decreased as treatment lines progressed (mean ± SD progression time: 523.2 ± 279.1 days from 1st to 2nd line, 351.6 ± 194.4 days from 2nd to 3rd line; 272.7 ± 139.3 days from 3rd to 4th + line). Significant HRU differences were found with subsequent treatment lines, including an increase in hospital admissions and patients on sick leave. Mean (95% CI) adjusted total costs per patient were €2974/year (2773–3175) in the 1st line and €5735/year (5043–6428) in the 4th + line. There was an increase in adjusted direct and total costs with subsequent treatment lines; the mean difference in total costs between cohorts was €2761 (p < 0.001). The highest direct costs were associated with epilepsy medication, days at the hospital and specialist visits.ConclusionOur data revealed a progressive increase in the use of resources and associated costs across subsequent epilepsy treatment lines.

COMORBIDITY AND CAUSE OF DEATH IN THE DIFFERENT VARIANTS OF SARS-COV-2 VIRUS, WITH CONTRIBUTION OF 20 AUTOPSY CASES

Analyzing the clinical and epidemiological data of COVID-19 suggests that specific comorbidities increase the risk of infection leading to worse lung injury and an even higher risk of death. The most common comorbidities reported up till now are hypertension, cardiovascular diseases, and diabetes. Aim to study: The design of the study includes comorbidity of patients and cause of death in alfa, delta, and omicron variants of SARS-CoV-2 virus, histological changes in the lungs, thrombotic complications of coronavirus infection and laboratory tests concerning thrombotic changes. Materials and Methods: We systematically evaluated 20 autopsies of patients deceased by COVID-19 infection. Collecting data was from February 28th, 2020, until June 2022. The cases were diagnosed with a PCR (Polymerase Chain Reaction) test and a rapid antigen test. 10 of the deceased patients were from the first, second, third, and fourth wave (I group) infected predominantly with the alfa and delta variants of coronavirus (from March 2020 until October 2021), and 10 patients infected after that date with predominantly the omicron variant (II group). Results: Most patients were over 50 years of age with multiple co-morbidities (28-88, average 63.9). Post-mortem case studies have shown Arterial hypertension in 80% (I/II gr), 60%/90% of patients with chronic ischemic heart disease, chronic and acute ischemic brain disease in 30%/10%, atherosclerosis, 60%/90%, diabetes mellitus 30%/40%, obesity stage III, 100%/95%). Clinical laboratory studies, in connection with thrombotic complications, revealed the increased value of creatine kinase, fibrinogen, D-dimers, and CRP. Lymphopenia was observed in 60%.All of the cases with COVID-19 viral desquamative pneumonia, at different stages, developed vascular thrombosis in medium-sized pulmonary vessels. Two patients developed pulmonary thromboembolism. We established 5 patients with generalized thrombosis. Three patients were complicated by infarcts in the brain, kidney, and spleen. Conclusion: The autopsies revealed a consistent pattern of pulmonary alveolar damage and generalized vascular/thrombotic disease in patients with frequent co-morbidities. The high frequency of generalized thrombotic complications was observed in predominant alfa and delta variants of the infection, while in the group with the omicron prevailing variant, the lung lesions were dominant, without extrapulmonary thrombotic complications, which we explain by the effective antithrombotic therapy. Major complications in these patients were secondary bacterial infection, sepsis, and respiratory distress syndrome.

Addiction Dispelling Myths

Addiction is a major public health problem and millions of people die due to addiction (nicotine, alcohol, and drugs of abuse). The economic consequences of drug addiction are staggering all over the World. Although great strides have been made in understanding the nature of addiction, it is still not well understood. Drug addiction can be considered a chronic brain disease that affects neurotransmission between circuits of neurons that control behavior, emotion and cognition; character­ized by an excessive engagement in drug use, unsuccessful attempts in controlling drug intake, an increase in anxiety and emotional pain, and inaccurate beliefs about drug use [1]. It is a chronically relapsing disorder characterized by: (a) compulsion to seek and take the drug, (b) loss of control in limiting intake and (c) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented.

Dynamics of indicators of motor functions on the background of physical rehabilitation in children of early age with epilepsy and motor disorders

Epilepsy is a chronic brain disease and one of the most common neurological diseases in the world, manifested by sudden seizures due to increased paroxysmal activity of neurons. There are no published studies aimed at assessing the dynamics of motor development in young children suffering from epilepsy with motor disorders.Purpose. The paper aimed at studying the dynamics of motor function indicators in patients with epilepsy on the background of movement disorders during three courses of rehabilitation treatment.Material and methods. We studied 123 young children with epilepsy and motor disorders. Age ranged from 9 months to 24 months. All patients were divided into 3 groups: group 1 patients who received only general massage, group 2: patients who received Vojta therapy, group 3: patients who received massage and Vojta therapy. The duration of remission for clinical seizures in all groups was at least 3 months, remission for video EEG monitoring in all patients was 23 months. Three courses of medical rehabilitation were carried out with an interval of 2 to 5 months for 1015 sessions of 2530 minutes daily. The dynamics of motor development of patients and the effectiveness of medical rehabilitation were assessed using the GMFCS scale, before and after each course of medical rehabilitation.Results. After the first course of rehabilitation, almost no improvement was observed and was unreliable, while after the second course there was a significant positive trend, especially pronounced in group 3. At the same time, the growth of the scale indicators in the period from the end of the first course to the end of the third was almost linear.Conclusion. The data obtained indicate the presence of a certain rigidity of the motor system of such patients, which determines the minimum dynamics after the first course of rehabilitation. Only starting from the second course, we begin to notice a linear improvement in the indicators of motor functions. The preferred duration of the interval between courses, in our opinion, is not less than two and not more than three months.

Automatic seizure detection and classification using super-resolution superlet transform and deep neural network -A preprocessing-less method

ContextEpilepsy, characterized by recurrent seizures, is a chronic brain disease that affects approximately 50 million. Recurrent seizures characterize it. A seizure, a burst of uncontrolled electrical activity between brain cells, results in temporary changes in behavior, level of consciousness, and involuntary movements. An accurate prediction of seizures can improve the standard of living in epileptic subjects. The increasing capabilities of machine learning and computer-assisted devices can detect seizures accurately with minimal human intervention. Proposed approachThis paper proposes a method to detect seizure and non-seizure events using superlet transform (SLT) and a deep convolution neural network: VGG-19. The electroencephalogram (EEG) dataset from the University of Bonn is used to validate the efficacy of the proposed method. MethodologySLT, a high-resolution time-frequency technique, converts EEG records into two-dimensional (2-D) images. SLT provides a high-resolution time-frequency representation reflecting the oscillation bursts in an EEG record. The time-frequency representations as 2-D images are fed to a pre-trained convolutional neural network: VGG-19. The last layers of VGG-19 are replaced with new layers to accommodate the different classification problems. ResultsThe proposed method achieved an accuracy of 100% for all seven seizure and non-seizure detection cases considered in this work. In the case of three and five-class classification problems, the proposed method has better accuracy than other existing methods. The CHB-MIT scalp EEG database is also used to assess the effectiveness of the proposed method, which achieved a classification accuracy of 94.3% in distinguishing between seizure and non-seizure events. ConclusionThe results obtained using the proposed methodology show the efficacy of the proposed method in accurately detecting seizures and other brain activity with the least pre-processing and human involvement. The proposed method can assist medical practitioners by saving their effort and time.

Epilepsy in literature

This paper represents a unique study carried out by a team of physicians having diverse medical experience (practitioners, residents, students), who relying on own viewpoints positions came to a common understanding and began to consider epilepsy not only as a severe, chronic, and widespread brain disease, but also as a part of human culture reflected in many literary works. Our study was aimed at searching and analyzing available sources that describe a course of epilepsy and its impact on life of famous people as well as its role in society. Literary images created in diverse centuries and eras by writers who personally suffered from epilepsy (F.M. Dostoevsky, Edgar Allan Poe, Wilkie Collins, and many others) turned out to be so colorful and convincing that they sometimes anticipated appearance of the first descriptions in professional medical literature, and even lay down in their basis.

Kalirin is involved in epileptogenesis by modulating the activity of the Rac1 signaling pathway

Background and objectiveEpilepsy is a common chronic brain disease. Despite the availability of various anti-seizure drugs, approximately 30 % of patients do not respond to treatment. Recent research suggests that Kalirin plays a role in regulating neurological function. However, the pathogenesis of Kalirin in epileptic seizures remains unclear. This study aims to investigate the role and mechanism of Kalirin in epileptogenesis. Materials and methodsAn epileptic model was induced by intraperitoneal injection of pentylenetetrazole (PTZ). Endogenous Kalirin was inhibited using shRNA. The expression of Kalirin, Rac1, and Cdc42 in the hippocampal CA1 region was measured using Western blotting. Spine and synaptic structures were examined using Golgi staining and electron microscopy. Moreover, the necrotic neurons in CA1 were examined using HE staining. ResultsThe results indicated that the epileptic score increased in epileptic animals, while inhibition of Kalirin decreased the epileptic scores and increased the latent period of the first seizure attack. Inhibition of Kalirin attenuated the increases in Rac1 expression, dendritic spine density, and synaptic vesicle number in the CA1 region induced by PTZ. However, the increase in Cdc42 expression was not affected by the inhibition of Kalirin. ConclusionThis study suggests that Kalirin is involved in the development of seizures by modulating the activity of Rac1, providing a novel anti-epileptic target.

The Pathogenesis of Epilepsy

Epilepsy, a group of chronic brain diseases characterized by different level of dysfunction of movement, sense, consciousness and autonomic nerve. The most common factors include: genetic factors, injury of brain cell and so on. At the molecular level, the imbalance between inhibition and excitation is considered as a concrete mechanism. When the ion channels on membrane change, the flow of ions will be interfered so that the excitability of cells will change, probably leading to epilepsy. Also, when the production of neurotransmitters goes wrong, normally the amount of inhibitory transmitter like GABA declines, and neurons will be over-excited. In addition, other reasons like parasite infection can also lead to epilepsy. This review aims to summarize the literatures investigating the relationship between different ion channels and epilepsy and the influence of excitatory and inhibitory neurotransmitters on epilepsy. This article does not only illustrate possible reasons causing epilepsy but, for each related channel or receptor protein, the basic information, subunit of protein and physiological function will be also covered in the review. The purpose of this article is to sort out the current researches on the pathogenesis of epilepsy so that people can have a comprehensive grasp of this field.

Eucommiae Folium and Active Compounds Protect Against Mitochondrial Dysfunction-Calcium Overload in Epileptic Hippocampal Neurons Through the Hypertrophic Cardiomyopathy Pathway.

Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy.

Brain glucose metabolism and dopamine transporter changes in rats with morphine-induced conditioned place preference.

Addiction to morphine is a chronic brain disease leading to compulsive abuse. Drug addiction animal models with and without conditioned place preference (CPP) training have been used to investigate cue-elicited drug craving. We used 18 F-fluorodeoxyglucose (18 F-FDG) and 11 C-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane (11 C-CFT) micro-PET/CT scans to examine the regional changes in brain glucose metabolism and dopamine transporter (DAT) availability to study their relationship underlying drug memory in morphine-treated rat models with and without CPP. Standardized uptake value ratio (SUVr) of 18 F-FDG significantly decreased in the medial prefrontal cortex (mPFC) and cingulate with short-term morphine administration compared with the baseline condition. Voxelwise analysis indicated glucose metabolism alterations in the somatosensory cortex, hippocampus and cingulate in morphine-treated rats and in the striatum, thalamus, medial prefrontal cortex, primary motor cortex and many regions in the cortex in the CPP group compared with the baseline condition. Alterative glucose metabolism was also observed in the striatum, primary somatosensory cortex and some cortical regions in the CPP group compared with morphine alone group. DAT expression alterations were only observed in the long-term morphine compared with the short-term morphine group. This study shows that cerebral glucose metabolism significantly altered during morphine administration and CPP process mainly in the mPFC, striatum and hippocampus, which indicates that the function of these brain regions is involved in cue-induced craving and memory retrieval.

Alpha-linolenic acid enhances the facilitation of GABAergic neurotransmission in the BLA and CA1.

Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy, stroke, spinal cord injury, traumatic brain injury, schizophrenia, and autism spectrum disorders. Underlying mechanisms are diverse, but a functional impairment and loss of GABAergic inhibitory neurons are common features in many of these disorders. While novel therapies abound to correct for the loss of GABAergic inhibitory neurons, it has been difficult at best to improve the activities of daily living for the majority of patients. Alpha-linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid found in plants. ALA exerts pleiotropic effects in the brain that attenuate injury in chronic and acute brain disease models. However, the effect of ALA on GABAergic neurotransmission in hyperexcitable brain regions involved in neuropsychiatric disorders, such as the basolateral amygdala (BLA) and CA1 subfield of the hippocampus, is unknown. Administration of a single dose of ALA (1500 nmol/kg) subcutaneously increased the charge transfer of inhibitory postsynaptic potential currents mediated by GABAA receptors in pyramidal neurons by 52% in the BLA and by 92% in the CA1 compared to vehicle animals a day later. Similar results were obtained in pyramidal neurons from the BLA and CA1 when ALA was bath-applied in slices from naïve animals. Importantly, pretreatment with the high-affinity, selective TrkB inhibitor, k252, completely abolished the ALA-induced increase in GABAergic neurotransmission in the BLA and CA1, suggesting a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Addition of mature BDNF (20 ng/mL) significantly increased GABAA receptor inhibitory activity in the BLA and CA1 pyramidal neurons similar to the results obtained with ALA. ALA may be an effective treatment for neuropsychiatric disorders where hyperexcitability is a major feature.

The Immunopathy of Alzheimer's Disease: Innate or Adaptive?

Beyond the time-honoured targeting of protein misfolding and aggregation, Alzheimer's disease needs new, innovative therapeutic directions. When exploring alternative druggable mechanisms, multifaceted in vitro and in vivo data demonstrate that immune system dysfunction is a pivotal driver of Alzheimer's disease progression. In pursuing neuroimmunological targets, a major but often under-discussed consideration regards the issue of whether innate or adaptive immunity (or both) within the neuroimmune network should be the centre of focus when devising immunotherapeutic approaches to Alzheimer's. This perspective article briefly reviews current data, concluding that while both innate and adaptive immunity contributes to the immunopathology of Alzheimer's, the pro-inflammatory microglia and cytokines of innate immunity will provide higher yield targets with a greater likelihood of efficacy. Although it seems paradoxical to focus on a rapid, short-lived aspect of immunity when seeking approaches to a quintessentially chronic brain disease, accumulating evidence affords ample data to support the target-rich cascade of innate immunity for the development of much-needed new diagnostics and therapeutics.

NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases—An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes

Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent Literature about this topic. First, we update conditions and mechanisms, including RNAs, extracellular vesicles/exosomes, endogenous compounds, and ethnic/pharmacological agents/extracts regulating NLRP3 function. Second, we pinpoint NLRP3-activating mechanisms and known NLRP3 inhibition effects in acute (ischemia, stroke, hemorrhage), chronic (Alzheimer's disease, Parkinson's disease, Huntington's disease, MS, ALS), and virus-induced (Zika, SARS-CoV-2, and others) human brain diseases. The available data show that (i) disease-specific divergent mechanisms activate the (mainly animal) brains NLRP3; (ii) no evidence proves that NLRP3 inhibition modifies human brain diseases (yet ad hoc trials are ongoing); and (iii) no findings exclude that concurrently activated other-than-NLRP3 inflammasomes might functionally replace the inhibited NLRP3. Finally, we highlight that among the causes of the persistent lack of therapies are the species difference problem in disease models and a preference for symptomatic over etiologic therapeutic approaches. Therefore, we posit that human neural cell-based disease models could drive etiological, pathogenetic, and therapeutic advances, including NLRP3's and other inflammasomes' regulation, while minimizing failure risks in candidate drug trials.

Predicting epileptic seizures based on EEG signals using spatial depth features of a 3D-2D hybrid CNN.

Epilepsy is a recurrent chronic brain disease that affects nearly 75 million people around the world. Therefore, the ability to reliably predict epileptic seizures would be instrumental for implementing interventions to reduce brain injury and improve patients' quality of life. In addition to classical machine learning algorithms and feature engineering methods, the use of electroencephalography (EEG) to predict seizures has gradually become a mainstream trend. Here, we propose a patient-specific method to predict epileptic seizures based on EEG data acquired using spatial depth features of a three-dimensional-two-dimensional hybrid convolutional neural network (3D-2D HyCNN) model. This method facilitates the acquisition of abundant and reliable deep features from multi-channel EEG signals. We first developed a reliable data preprocessing method to reconstruct time-series EEG signals into 3D feature images. Then, the 3D-2D HyCNN model was used to extract correlation features between multiple channels of EEG signals, which are automatically exploited by the network to improve seizure prediction. The method achieved accuracy of 98.43% and 93.11%, sensitivity of 98.58% and 90.98%, and specificity of 96.86% and 92.39% on the CHB-MIT Scalp EEG dataset and the American Epilepsy Society Epilepsy Prediction Challenge dataset, respectively. The results revealed that the new algorithm is reliable. Graphical Abstract A new patient-specific epilepsy prediction approach.

Analysis of the influence of positive psychotherapy on the improvement of re drinking among alcohol dependent people from the perspective of ideology and politics

BackgroundAlcohol dependence is a chronic and recurrent brain disease of central nervous system poisoning caused by long-term excessive drinking. The prevalence of alcohol-dependence patients in China shows a rising trend year by year. Alcohol dependence will not only cause serious harm to patients’ physical health and mental state, but also affect their family relations and even entire social security. The study evaluated the improvement of psychological intervention measures on alcohol-dependent people’s rehydration in the context of the Great Thought Policy to help them better reduce alcohol dependence.Subjects and MethodsThe study selected 200 patients with alcohol dependence admitted to a provincial hospital. The patients were divided into an experimental group and a control group by the random number table method. Both groups were treated with the same drug intervention. Among them, the patients in the experimental group were treated under active psychotherapy, that is, the responsible nurse combined psychological knowledge with ideological guidance to guide the patients to quit drinking. The control group was given routine psychological intervention. The patients were investigated with Symptom Checklist 90 (SCL-90) and telephone follow-up. The data were processed with SPSS 17.0 statistical software, and P &lt; 0.05 indicated that the difference was statistically significant.ResultsResults showed that the rehydration rate and rehospitalization rate of the experimental group were lower than those of the control group, and the mental health status of the patients in the experimental group was significantly improved compared with the control group (P &lt; 0.05), indicating that the psychological measures under the ideological and political intervention can effectively control the patients’ emotions.Table 1.Comparison of rehydration rate, rehospitalization rate and psychological status of patients before and after the treatmentGroupsRehydration rateRehospitalization rateRehospitalization rate of rehydrationSCL-90Experimental group22 (22.00%)19 (19.00%)19/22 (86.36%)10.23±0.33Control group24 (24.00%)21 (21.00%)21/24 (87.50%)18.24±0.78χ2 values4.2623.2850.3963.298P values0.0040.0320.0410.002ConclusionsThe experimental results show that the combination of ideological guidance and positive psychological knowledge, and the guidance and intervention of patients can effectively reduce their alcohol relapse, improve the level of mental health, and achieve the effect of successful abstinence.

Development and Psychometric Properties of a health-promoting self-care behavior scale (HPSCB-S) in recovered patients from Drug Addiction

Background and objectivesDrug addiction is a chronic and relapsing brain disease. Practicing self-care is one of the rules offered by therapists to improve the withdrawal process and prevent relapse. Based on the evidence, health beliefs, including Pender’s proposed model, are significantly effective in adopting self-care behaviors in patients. On the other hand, in order to evaluate preventive interventions regarding drug use and relapse of drug use; Having a good and appropriate tool is a special priority. Therefore, the present study aims to design and determine the psychometric characteristics of the questionnaire for measuring health-promoting self-care behaviors in patients recovered from drug addiction has been carried out in the west of Mazandaran province.MethodsThe current study is a cross-sectional descriptive methodological research. In the first stage, the items and primary classes of the new tool were extracted based on the review of studies consistent with Pender’s self-care promotion and a questionnaire was designed. In the second stage, the psychometric characteristics of the designed questionnaire were examined using face validity, content validity, construct validity and reliability. In the construct validity, the number of participants was 245 for exploratory factor analysis and 203 for confirmatory factor analysis. In the reliability test, 25 people participated to check internal consistency and test-retest. Random sampling was done from 12 drug addiction treatment clinics in two cities of Tonkabon and Ramsar in the west of Mazandaran province during 2021–2022. Data were analyzed using SPSS and AMOS software version 23.ResultsThe exploratory factor analysis revealed 7 factors containing 29 item explained more than 61% of the total observed variance. The results of confirmatory factor analysis showed that the data fit the model. In the reliability test, Cronbach’s alpha coefficient indicated the appropriate internal consistency of the tool and retesting the tool with an interval of 2 weeks showed acceptable stability of the tool.ConclusionThe present study showed that the researcher-made questionnaire has good validity and reliability and can be used to measure self-care behaviors of patients who have recovered from addiction in order to provide appropriate solutions to prevent the relapse of drug use.

Supporting brain health in multiple sclerosis: exploring the potential of neuroeducation combined with practical mindfulness exercises in the management of neuropsychological symptoms

ObjectiveWe aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit.MethodsBoth interventions were administered in small groups of ambulatory patients. Neuropsychological testing before and after the 3- to 4-week intervention phase comprised patient reported outcomes and cognitive tests. After 3, 6 and 12 months, participants completed online surveys. Analysis of change scores (between baseline and retest) with t-tests (Mann–Whitney U and Wilcoxon tests, respectively) and mixed ANCOVAs with repeated measures for comparison of both interventions were conducted.ResultsA total of 65 pwpMS turned to a final sample of 50 (n = 15 excluded due to drop-outs, occurrence of relapse or steroid treatment). Change scores within MaTiMS revealed no significant effect on the PDQ-20 total score and only a significant effect on the subscale retrospective memory lasting 3 months with a moderate effect size. In contrast, MaTiMS-modified revealed a highly significant change in PDQ-20 total compared to baseline and significant improvements with small to moderate effect sizes on all PDQ-20 subscales (lasting until 3 months), in self-efficacy, stress, visuo-spatial working memory (moderate effect sizes), and fatigue (small effect size). While no interaction effect between time and group could be revealed, a significant main effect for time was found in PDQ-20 total.ConclusionBoth MaTiMS and MaTiMS-modified positively affected perceived cognitive deficits. However, our data speak in favor of additional benefits by adding neuroeducational and mindfulness-based exercises thus being valuable methods to support brain health including self-efficacy, perceived stress, and fatigue, even in patients with a chronic and progressive brain disease.

Neurostimulation as a Putative Method for the Treatment of Drug-resistant Epilepsy in Patient and Animal Models of Epilepsy.

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy.

Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis.

Epilepsy is one of the most common chronic brain diseases. Almost one-third of patients have drug-resistant epilepsy (DRE). Cannabidiol is being considered as a potential novel drug for treating DRE. To investigate long-term efficacy and safety of cannabidiol in treatment of DRE and the differences in cannabidiol treatment among patients with different characteristics. Systematic review and meta-analysis. Medline, Embase, and CENTRAL were searched for literature. RevMan5.4 was used for meta-analysis. The Intention-to-treat set and the random effect were used as the main analysis. Subgroup analyses were performed according to age, dose, concomitant antiseizure medications (ASMs), epilepsy syndromes, and study designs. Fifty studies were included in this systematic review. A total of 4791 participants were collected. The responder rates (seizure frequency reduced at least 50%) at 12-, 24-, 48-, 72-, 96-, and 144-week were 0.40 [0.36, 0.45], 0.39 [0.34, 0.44], 0.37 [0.30, 0.44], 0.27 [0.17, 0.37], 0.22 [0.14, 0.30], and 0.38 [0.23, 0.53]. Seizure-free rates were 0.04 [0.03, 0.06], 0.04 [0.03, 0.05], 0.03 [0.02, 0.05], 0.03 [0.02, 0.03], 0.02 [0.01, 0.03], and 0.04 [0.01, 0.06]. Proportion of adverse events were 0.72 [0.61, 0.83], 0.62 [0.42, 0.81], 0.60 [0.41, 0.79], 0.35 [0.14, 0.56], 0.83 [0.75, 0.90], and 0.96 [0.94, 0.99]. The pooled 12-, 24-, 48-, 96-, and 144-week proportion of serious adverse events were 0.15 [0.09, 0.21], 0.23 [0.14, 0.31], 0.10 [0.06, 0.15], 0.31 [0.24, 0.38], and 0.40 [0.35, 0.45]. Subgroup analyses showed that there was no significant difference on efficacy and safety among age subgroups and epilepsy syndromes subgroups. For most periods, there were no significant difference on efficacy among subgroups of dose and concomitant ASMs. However, higher doses and more concomitant ASMs were associated with higher proportion of adverse events. Cannabidiol treatment of DRE has stable efficacy and fewer adverse events in early period. Long-term use may have decreased efficacy and increased adverse events. Dose escalation may not increase efficacy, but may increase adverse events. Furthermore, cannabidiol use may reduce dosage of other ASMs without reducing efficacy, thereby reducing adverse effects. Cannabidiol may have similar effects in various epilepsy syndromes. PROSPERO (CRD42022351250).