Chronic Neurological Disorder Research Articles

Alterations in Circadian Rhythms, Sleep, and Physical Activity in COVID-19: Mechanisms, Interventions, and Lessons for the Future.

Although the world is acquitting from the throes of COVID-19 and returning to the regularity of life, its effects on physical and mental health are prominently evident in the post-pandemic era. The pandemic subjected us to inadequate sleep and physical activities, stress, irregular eating patterns, and work hours beyond the regular rest-activity cycle. Thus, perturbing the synchrony of the regular circadianclock functions led to chronic psychiatric and neurological disorders and poor immunological response in several COVID-19 survivors. Understanding the links between the host immune system and viral replication machinery from a clock-infection biology perspective promises novel avenues of intervention. Behavioral improvements in our daily lifestyle can reduce the severity and expedite the convalescent stage of COVID-19 by maintaining consistent eating, sleep, and physical activity schedules. Including dietary supplements and nutraceuticals with prophylactic value aids in combating COVID-19, as their deficiency can lead to a higher risk of infection, vulnerability, and severity of COVID-19. Thus, besides developing therapeutic measures, perpetual healthy practices could also contribute to combating the upcoming pandemics. This review highlights the impact of the COVID-19 pandemic on biological rhythms, sleep-wake cycles, physical activities, and eating patterns and how those disruptions possibly contribute to the response, severity, and outcome of SARS-CoV-2 infection.

Application and Effectiveness of Dietary Therapies for Pediatric Migraine

Migraine is a representative type of primary headache and a common chronic neurological disease that accounts for a large proportion of headaches in children, adolescents, and adults. Unlike migraine in adulthood, pediatric migraine occurs when brain development is not yet complete. This characteristic may require a new perspective for the treatment and management of pediatric migraine. Dietary therapies, mainly the ketogenic diet and its variants, can have positive effects on pediatric migraine. Several recent studies have revealed that dietary therapies, such as the classic ketogenic diet, modified Atkins diet, and low glycemic index diet, improve various neurological diseases by improving dysbiosis of microbiota, reducing proinflammatory cytokines, and increasing mitochondrial function. Nonetheless, the mechanism through which active dietary therapy affects pediatric migraine requires further research. To achieve this, an important role is played by the neuro-nutritional team, which can develop and manage tolerable diets for pediatric migraine patients through mutual collaboration among pediatric neurologists, nurses, and nutritionists.

Common Ground: We Can Comprehensively Treat Pediatric Epilepsy and Psychiatric Comorbidities

Epilepsy and psychiatric illness have been long studied and today are better accepted as co-occurring than as discrete illnesses that are independent even if associated. Common pathophysiology may not be easily explained, but clearly exists given the significant overrepresentation of psychiatric illness among individuals with epilepsy. Conditions like autism spectrum disorder, anxiety, depression, and attention deficit hyperactivity disorder are prevalent in pediatric epilepsy much more than expected, even in the context of chronic neurologic disease. The interplay between pediatric epilepsy and neuropsychiatric symptoms represents a complex clinical circumstance that is not well subtended by the chasm-like division of labor between psychiatrists and neurologists. The unfortunate result is that children and families often experience care that is fractured and at worst, counterproductive for their quality of life. A neuropsychiatric paradigm is essential to address epilepsy and its intrinsic psychiatric symptoms. Practical strategies will be discussed to address this challenge.

Differentiating Epileptic and Psychogenic Non-Epileptic Seizures Using Machine Learning Analysis of EEG Plot Images

The treatment of epilepsy, the second most common chronic neurological disorder, is often complicated by the failure of patients to respond to medication. Treatment failure with anti-seizure medications is often due to the presence of non-epileptic seizures. Distinguishing non-epileptic from epileptic seizures requires an expensive and time-consuming analysis of electroencephalograms (EEGs) recorded in an epilepsy monitoring unit. Machine learning algorithms have been used to detect seizures from EEG, typically using EEG waveform analysis. We employed an alternative approach, using a convolutional neural network (CNN) with transfer learning using MobileNetV2 to emulate the real-world visual analysis of EEG images by epileptologists. A total of 5359 EEG waveform plot images from 107 adult subjects across two epilepsy monitoring units in separate medical facilities were divided into epileptic and non-epileptic groups for training and cross-validation of the CNN. The model achieved an accuracy of 86.9% (Area Under the Curve, AUC 0.92) at the site where training data were extracted and an accuracy of 87.3% (AUC 0.94) at the other site whose data were only used for validation. This investigation demonstrates the high accuracy achievable with CNN analysis of EEG plot images and the robustness of this approach across EEG visualization software, laying the groundwork for further subclassification of seizures using similar approaches in a clinical setting.

Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: implications for epileptogenesis and epilepsy.

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions of individuals worldwide. Despite extensive research, the underlying mechanisms leading to epileptogenesis, the process by which a normal brain develops epilepsy, remain elusive. We, here, explored the immune system and spleen responses triggered by pilocarpine-induced status epilepticus (SE) focusing on their role in the epileptogenesis that follows SE. Initial examination of spleen histopathology revealed transient disorganization of white pulp, in animals subjected to SE. This disorganization, attributed to immune activation, peaked at 1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheral blood lymphocyte populations, demonstrated a decrease following SE, accompanied by a reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundance of T-lymphocytes in the piriform cortex and choroid plexus at 3DPSE, suggesting a specific mobilization toward the Central Nervous System. Notably, splenectomy mitigated brain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularly in the hippocampus and piriform cortex. Additionally, splenectomized animals exhibited reduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomy correlated with improved neuronal survival, substantiated by decreased neuronal loss and reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE. Overall, these findings underscore the pivotal role of the spleen in orchestrating immune responses and neuroinflammation following pilocarpine-induced SE, implicating the peripheral immune system as a potential therapeutic target for mitigating neuronal degeneration in epilepsy.

The European Academy of Neurology NeuroCOVID-19 Task Force: A lesson for the future.

The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.

Development of the pediatric narcolepsy patient-reported outcomes scale (PN-PROs)

BackgroundPediatric narcolepsy is a chronic neurological disorder that impacts the health and overall wellbeing of children and adolescents with the disease. Meaningful and regular assessment of symptom frequency and severity is important for the long-term management of narcolepsy and for optimizing quality of life. However, there is currently no patient-reported outcomes (PROs) measure developed from both patient and expert input that is designed specifically to assess the impact of pediatric narcolepsy on daily life and overall disease burden.MethodsWe conducted a qualitative mixed-methods study to develop a novel patient-reported outcomes measure for pediatric narcolepsy patients. We created and refined a conceptual framework through literature review, semi-structured interviews with narcolepsy experts, and focus groups of children and adolescents with narcolepsy and their parents. Guided by the domains and facets identified in our conceptual framework and further literature review, we developed a PROs item bank. Our team further refined the item bank and classified items through team discussions and expert guidance. Content validity of the item pool was evaluated with expert review, readability analysis, and cognitive interviews with narcolepsy patients.ResultsThrough our processes, we developed a PROs item bank comprising two domains (narcolepsy symptoms and functional impairment) that contains 10 facets. The final item bank consists of 55 items, with 27 items representing five facets of narcolepsy symptoms (behavior, cataplexy, cognitive difficulties, sleep quality, and sleepiness) and 28 items representing five facets of functional impairment (bothered by/worried about symptom, cognitive/academic, global functioning, safety, and social).ConclusionWe developed items for the Pediatric Narcolepsy Patient-Reported Outcomes (PN-PROs) measure that incorporates expert insight, published literature, and testimony from children/adolescents living with narcolepsy and their families. Upon completion of the psychometric testing and content validation process, we believe the PN-PROs will provide a useful longitudinal measure of disease control and standardize outcome assessments in clinical practice and research studies.

The effect of the COVID-19 pandemic on the caregiving burden of individuals caring for patients with chronic neurological diseases.

Caring for neurological patients poses a serious burden on caregivers, even in normal times. It is likely that this burden has become even more painful post-COVID-19 pandemic. This study evaluates the effect of the COVID-19 pandemic on the care burden of those who care for patients with chronic neurological diseases. The study included 50 patients and 50 caregivers. All the tests were conducted twice, it was answered firstly, according to the pre-COVID-19 pandemic, and secondly, during the COVID-19 pandemic period. The depression levels of the patients and caregivers were assessed with the Beck Depression Scale, their sleep quality with the Pittsburgh Sleep Quality Index, their quality of life was assessed with the RAND 36-Item Health Survey, and caregivers' burden of care was evaluated with the Zarit Caregiver Burden Scale. It was observed at the end of the study that the depression levels of patients (p = 0.00), and caregivers (p = 0.00) increased post-COVID-19 pandemic, the sleep quality of caregivers (p = 0.00), and patients (p = 0.02) decreased post-COVID-19 pandemic. On the other hand, it was determined that caregivers' burden of care increased (p = 0.00). Sub-parameters of the RAND 36-Item Health Survey, physical functioning (p = 0.02), role limitations due to physical health (p = 0.00), and role limitations due to emotional problems (p = 0.03) decreased for caregivers. In summary, we concluded that the well-being and psychological status of both patients and their caregivers were adversely affected by the COVID-19 pandemic.

Fifty Years of Handedness Research: A Neurological and Methodological Update

Handedness, a complex human aspect that reflects the functional lateralization of the hemispheres, also interacts with the immune system. This study aimed to expand the knowledge of the lateralization of hand, foot, and eye activities in patients with immune-mediated (IM) or other (noIM) neurological diseases and to clarify the properties of the Edinburgh Handedness Inventory (EHI) in an Italian population. Three hundred thirty-four patients with IM or noIM diseases affecting the brain or spine and peripheral nervous system were interviewed about stressful events preceding the disease, subjective handedness, and familiarity for left-handedness or ambidexterity. The patients and 40 healthy subjects underwent EHI examination. In the whole group of participants, 24 items of the EHI were classified into five factors (Hand Transitive, Hand Refined, Hand Median, Foot, Eye), demonstrating good reliability and validity. Chronological age had a significant influence on hand and foot EHI factors and the laterality quotient (LQ), particularly on writing and painting. In the patient groups, EHI factors and the LQ were also predicted by age of disease onset, duration of disease, and family history of left-handedness or ambidexterity. No differences were found between patients and healthy subjects, but pencil use scored significantly lower in patients with IM diseases than in those with noIM brain diseases. These results demonstrate that the lateralization of hand and foot activities is not a fixed human aspect, but that it can change throughout life, especially for abstract and symbolic activities. Chronic neurological diseases can cause changes in handedness. This may explain why, unlike systemic immunological diseases, IM neurological diseases are not closely associated with left-handedness. In these patients, the long version of the EHI is appropriate for determining the lateralization of body activities to contextualize the neurological picture; therefore, these findings extend the Italian normative data sets.

The functional and molecular roles of p75 neurotrophin receptor (p75NTR) in epilepsy.

Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75NTR in epilepsy.

Dysphagia in neuromyelitis optica spectrum disorder and multiple sclerosis: A comparison of frequency, severity, and effects on quality of life

OverviewDysphagia has been previously discussed as a potential life-threatening condition secondary to chronic neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, its impact on the quality of life (QoL) of patients with NMOSD has never been studied before. This study aims to determine the frequency of dysphagia and its impact on QoL in NMOSD patients in comparison with MS people and healthy individuals. MethodsSeventy-five MS and sixty-five NMOSD patients with an expanded disability status scale (EDSS) score ≥ 3.5 in addition to 106 healthy controls were enrolled in this cross-sectional study. All the participants completed the self-report dysphagia in MS (DYMUS) and 36-item short-form health survey (SF-36) questionnaires. In case of positive answers to at least one of the questions in DYMUS, they were asked to fill out the dysphagia handicap index (DHI) questionnaire. ResultsThe frequency of dysphagia in NMOSD, MS, and control groups was 61.54 %, 72.97 %, and 27 %, respectively. Patients with swallowing problems had reduced scores across different swallowing-related QoL domains compared to non-dysphagic patients (p < 0.05). NMOSD (1, IQR [0–3.5]) and MS patients (2, IQR [0–4]) had a significantly higher median total DYMUS score than control (0, IQR [0–1]) (p < 0.01). However, there was no discernible difference between the two patient groups. NMOSD had the highest mean total DHI score (21.22 ± 21), followed by MS (15.25 ± 18.94) and control (7.08 ± 5.12). A significant correlation was seen in the NMOSD group between the DHI total score and the SF-36 total score (r = 0.62, p < 0.05). The DHI and SF-36 subscales showed a strong association as well. The overall SF-36 scores in both the control and MS groups was not significantly correlated with DHI. The generalized linear model analysis showed that the NMOSD group's age (p-value = 0.005), EDSS (p-value < 0.001), and total DYMUS score (p-value = 0.018) significantly affected overall health status. ConclusionThe presence of dysphagia significantly impacts the QoL in NMOSD patients, particularly in aspects related to swallowing. These findings underscore the critical need for diligent dysphagia screening and emphasize the importance of educating both caregivers and NMOSD patients about managing this challenging symptom.

Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice.

Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.

In vitro human cell culture models in a bench-to-bedside approach to epilepsy.

Epilepsy is the most common chronic neurological disease, affecting nearly 1%-2% of the world's population. Current pharmacological treatment and regimen adjustments are aimed at controlling seizures; however, they are ineffective in one-third of the patients. Although neuronal hyperexcitability was previously thought to be mainly due to ion channel alterations, current research has revealed other contributing molecular pathways, including processes involved in cellular signaling, energy metabolism, protein synthesis, axon guidance, inflammation, and others. Some forms of drug-resistant epilepsy are caused by genetic defects that constitute potential targets for precision therapy. Although such approaches are increasingly important, they are still in the early stages of development. This review aims to provide a summary of practical aspects of the employment of invitro human cell culture models in epilepsy diagnosis, treatment, and research. First, we briefly summarize the genetic testing that may result in the detection of candidate pathogenic variants in genes involved in epilepsy pathogenesis. Consequently, we review existing invitro cell models, including induced pluripotent stem cells and differentiated neuronal cells, providing their specific properties, validity, and employment in research pipelines. We cover two methodological approaches. The first approach involves the utilization of somatic cells directly obtained from individual patients, while the second approach entails the utilization of characterized cell lines. The models are evaluated in terms of their research and clinical benefits, relevance to the invivo conditions, legal and ethical aspects, time and cost demands, and available published data. Despite the methodological, temporal, and financial demands of the reviewed models they possess high potential to be used as robust systems in routine testing of pathogenicity of detected variants in the near future and provide a solid experimental background for personalized therapy of genetic epilepsies. PLAIN LANGUAGE SUMMARY: Epilepsy affects millions worldwide, but current treatments fail for many patients. Beyond traditional ion channel alterations, various genetic factors contribute to the disorder's complexity. This review explores how invitro human cell models, either from patients or from cell lines, can aid in understanding epilepsy's genetic roots and developing personalized therapies. While these models require further investigation, they offer hope for improved diagnosis and treatment of genetic forms of epilepsy.

Joint transformer architecture in brain 3D MRI classification: its application in Alzheimer's disease classification.

Alzheimer's disease (AD), a neurodegenerative disease that mostly affects the elderly, slowly impairs memory, cognition, and daily tasks. AD has long been one of the most debilitating chronic neurological disorders, affecting mostly people over 65. In this study, we investigated the use of Vision Transformer (ViT) for Magnetic Resonance Image processing in the context of AD diagnosis. ViT was utilized to extract features from MRIs, map them to a feature sequence, perform sequence modeling to maintain interdependencies, and classify features using a time series transformer. The proposed model was evaluated using ADNI T1-weighted MRIs for binary and multiclass classification. Two data collections, Complete 1Yr 1.5T and Complete 3Yr 3T, from the ADNI database were used for training and testing. A random split approach was used, allocating 60% for training and 20% for testing and validation, resulting in sample sizes of (211, 70, 70) and (1378, 458, 458), respectively. The performance of our proposed model was compared to various deep learning models, including CNN with BiL-STM and ViT with Bi-LSTM. The suggested technique diagnoses AD with high accuracy (99.048% for binary and 99.014% for multiclass classification), precision, recall, and F-score. Our proposed method offers researchers an approach to more efficient early clinical diagnosis and interventions.

Enhancing Epilepsy Awareness and Cooperative Care in Elementary and Middle Schools

Epilepsy, a prevalent chronic neurological disorder, presents numerous challenges for people with epilepsy (PWEs) and their caregivers. They experience difficulties in receiving proper care and support due to stigma and misconceptions. Promoting public awareness in early education would be critical to reduce the stigma and to properly support them. We conducted 145 surveys and 21 interviews with teachers, school nurses, and parents of elementary and middle school students. While the participants exhibited slightly positive attitudes towards PWEs, we identified obstacles that hinder learning about epilepsy and seizure first aid: inadequate education and limited information sharing among school stakeholders. Moreover, there is a pressing need for age-appropriate education that considers the students' ages and perceptual levels. Considering the current limitations and needs, we propose potential implications for future information and communication technologies (ICTs) designs, including knowledge-sharing systems and an educational game aimed at enhancing epilepsy awareness and fostering collaborative care in elementary and middle school environments.

The suppressive effect of the specific KCC2 modulator CLP290 on seizure in mice

Epilepsy is a chronic neurological disorder characterized by episodic dysfunction of central nervous system. The most basic mechanism of epilepsy falls to the imbalance between excitation and inhibition. In adults, GABAA receptor (GABAAR) is the main inhibitory receptor to prevent neurons from developing hyperexcitability, while its inhibition relies on the low intracellular chloride anion concentration ([Cl-]i). Neuronal-specific electroneutral K+-Cl− cotransporter (KCC2) can mediate chloride efflux to lower [Cl-]i for GABAAR mediated inhibition. Our previous study has revealed that the coordinated downregulation of KCC2 and GABAAR participates in epilepsy. According to a high-throughout screen for compounds that reduce [Cl−]i, CLP290 turns out to be a specific KCC2 functional modulator. In current study, we first confirmed that CLP290 could dose-dependently suppress convulsant-induced seizures in mice in vivo as well as the epileptiform burst activities in cultured hippocampal neurons in vitro. Then, we discovered that CLP290 functioned through preventing the downregulation of the KCC2 phosphorylation at Ser940 and hence the KCC2 membrane expression during convulsant stimulation, and consequently restored the GABA inhibition. In addition, while CLP290 was given in early epileptogenesis period, it also effectively decreased the spontaneous recurrent seizures. Generally, our current results demonstrated that CLP290, as a specific KCC2 modulator by enhancing KCC2 function, not only inhibits the occurrence of the ictal seizures, but also suppresses the epileptogenic process. Therefore, we believe KCC2 may be a suitable target for future anti-epileptic drug development.

Risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly patients infected with the Omicron variant of SARS-CoV-2: a retrospective study at Shanghai Fourth People's Hospital, School of Medicine, Tongji University.

In elderly patients infected with the Omicron variant, disease progression to severe infection can result in poor outcomes. This study aimed to identify risk and protective factors associated with disease progression to severe infection and viral clearance time in elderly Omicron-infected patients. Shanghai Fourth People's Hospital, School of Medicine, Tongji University, was officially designated to provide treatment to patients with COVID-19. This study was conducted on confirmed Omicron cases admitted to the hospital between 10 April 2022 and 21 June 2022. In total, 1,568 patients aged 65 years or older were included. We conducted a retrospective, observational study using logistic regression to analyze risk and protective factors for the development of severe disease and Cox proportional hazards regression models to analyze factors influencing viral clearance time. Aged over 80 years, having 2 or more comorbidities, combined cerebrovascular disease, chronic neurological disease, and mental disorders were associated with the development of severe disease, and full vaccination was a protective factor. Furthermore, aged over 80 years, combined chronic respiratory disease, chronic renal disease, cerebrovascular disease, mental disorders, and high viral load were associated with prolonged viral clearance time, and full vaccination was a protective factor. This study analyzed risk factors for progression to severe infection and prolonged viral clearance time in hospitalized elderly Omicron-infected patients. Aged patients with comorbidities had a higher risk of developing severe infection and had longer viral clearance, while vaccination protected them against the Omicron infection.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

Investigating the Effects of Perampanel on Autophagy-mediated Regulation of GluA2 and PSD95 in Epilepsy.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite various treatment approaches, a significant number of patients continue to experience uncontrolled seizures, leading to refractory epilepsy. The emergence of novel anti-epileptic drugs, such as perampanel (PER), has provided promising options for effective epilepsy treatment. However, the specific mechanisms underlying the therapeutic effects of PER remain unclear. This study aimed to investigate the intrinsic molecular regulatory mechanisms involved in the downregulation of GluA2, a key subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, following epileptic seizures. Primary mouse hippocampal neurons were cultured and subjected to an epilepsy cell model. The expression levels of GluA2 and autophagy-related proteins were assessed using Western blotting and real-time fluorescent quantitative PCR. Immunofluorescence and immunohistochemistry techniques were employed to investigate the nuclear translocation of CREB-regulated transcriptional coactivator 1 (CRTC1). Additionally, status epilepticus animal models were established to further validate the findings. The epilepsy cell model exhibited a significant decrease in GluA2 expression, accompanied by elevated levels of autophagy-related proteins. Immunofluorescence analysis revealed the nuclear translocation of CRTC1, which correlated with the expression of autophagy-related genes. Treatment with an autophagy inhibitor reversed the decreased expression of GluA2 in the epilepsy cell model. Furthermore, the calcium/calmodulin-dependent protein phosphatase inhibitor FK506 and CaN overexpression affected the dephosphorylation and nuclear translocation of CRTC1, consequently influencing GluA2 expression. Animal model results further supported the involvement of these molecular mechanisms in epilepsy. Our findings suggest that the downregulation of GluA2 following epileptic seizures involves the activation of autophagy and the regulation of CRTC1 nuclear translocation. These intrinsic molecular regulatory mechanisms provide potential targets for developing novel therapeutic strategies to alleviate refractory epilepsy and preserve cognitive functions in patients.

Pediatric-adult Care Transition and Quality of Life in People with Multiple Sclerosis and Other Chronic Neurological Diseases: A Preliminary Study (P1-6.014)

Pediatric-adult Care Transition and Quality of Life in People with Multiple Sclerosis and Other Chronic Neurological Diseases: A Preliminary Study (P1-6.014)