M. Desforges, Alain Le Coupanec, Philippe Dubeau
et al.
Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.
Microglia, the resident macrophages of the central nervous system, rapidly activate in nearly all kinds of neurological diseases. These activated microglia become highly motile, secreting inflammatory cytokines, migrating to the lesion area, and phagocytosing cell debris or damaged neurons. During the past decades, the secretory property and chemotaxis of microglia have been well-studied, while relatively less attention has been paid to microglial phagocytosis. So far there is no obvious concordance with whether it is beneficial or detrimental in tissue repair. This review focuses on phagocytic phenotype of microglia in neurological diseases such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, traumatic brain injury, ischemic and other brain diseases. Microglial morphological characteristics, involved receptors and signaling pathways, distribution variation along with time and space changes, and environmental factors that affecting phagocytic function in each disease are reviewed. Moreover, a comparison of contributions between macrophages from peripheral circulation and the resident microglia to these pathogenic processes will also be discussed.
Gene transfer has long been a compelling yet elusive therapeutic modality. First mainly considered for rare inherited disorders, gene therapy may open treatment opportunities for more challenging and complex diseases such as Alzheimer's or Parkinson's disease. Today, examples of striking clinical proof of concept, the first gene therapy drugs coming onto the market, and the emergence of powerful new molecular tools have broadened the number of avenues to target neurological disorders but have also highlighted safety concerns and technology gaps. The vector of choice for many nervous system targets currently is the adeno-associated viral (AAV) vector due to its desirable safety profile and strong neuronal tropism. In aggregate, the clinical success, the preclinical potential, and the technological innovation have made therapeutic AAV drug development a reality, particularly for nervous system disorders. Here, we discuss the rationale, opportunities, limitations, and progress in clinical AAV gene therapy.
Neurological diseases continue to increase in prevalence worldwide. Combined with the lack of modifiable risk factors or strongly efficacious therapies, these disorders pose a significant and growing burden on healthcare systems and societies. The development of neuroprotective or curative therapies is limited by a variety of factors, but none more than the highly selective blood-brain barrier. Intranasal administration can bypass this barrier completely and allow direct access to brain tissues, enabling a large number of potential new therapies ranging from bioactive peptides to stem cells. Current research indicates that merely administering simple solutions is inefficient and may limit therapeutic success. While many therapies can be delivered to some degree without carrier molecules or significant modification, a growing body of research has indicated several methods of improving the safety and efficacy of this administration route, such as nasal permeability enhancers, gelling agents, or nanocarrier formulations. This review shall discuss promising delivery systems and their role in expanding the clinical efficacy of this novel administration route. Optimization of intranasal administration will be crucial as novel therapies continue to be studied in clinical trials and approved to meet the growing demand for the treatment of patients with neurological diseases.
Background: It is widely known that the harmful effects of fine dust can cause various diseases. Research on the correlation between fine dust and health has been mainly focused on lung and cardiovascular diseases. By contrast, the effects of air pollution on the central nervous system (CNS) are not broadly recognized. Findings: Air pollution can cause diverse neurological disorders as the result of inflammation of the nervous system, oxidative stress, activation of microglial cells, protein condensation, and cerebral vascular-barrier disorders, but uncertainty remains concerning the biological mechanisms by which air pollution produces neurological disease. Neuronal cell damage caused by fine dust, especially in fetuses and infants, can cause permanent brain damage or lead to neurological disease in adulthood. Conclusion: It is necessary to study the air pollution–CNS disease connection with particular care and commitment. Moreover, the epidemiological and experimental study of the association between exposure to air pollution and CNS damage is critical to public health and quality of life. Here, we summarize the correlations between fine dust exposure and neurological disorders reported so far and make suggestions on the direction future research should take.
Giulia Binarelli, Florence Joly, François Christy
et al.
Abstract Background This feasibility study evaluated adherence and effectiveness to a digital multimodal intervention (cognitive and physical training) for cancer-related cognitive impairment (CRCI) in patients with breast cancer. Methods Breast cancer patients undergoing radiotherapy and with significant cognitive complaints impacting quality of life participated in a 12-week intervention, combining non-simultaneous 20-min cognitive and 30-min physical sessions, twice weekly. Assessments included perceived cognitive impairment (PCI), objective cognition, fatigue, anxiety/depression, sleep and satisfaction. High level of adherence was defined as completing 9/12 weeks of the program. A week was complete when at least 70% of each of the planned sessions was completed. Physical activity intensity was defined by max age-related heart rate. Results Among 419 radiotherapy-treated patients with breast cancer, 170 had cognitive complaints (41%), 83 were eligible (49%), 29 were not included (35%) due to organizational issue and 20 among eligible contacted patients agreed to participate (37%). The majority of participants (48.3 ± 8 years of age) received chemotherapy (18/20) and 17 had I-II cancer stage. Eleven of twenty participants were highly adherent (higher adherence in physical (95%) than cognitive training (55%)). All expressed satisfaction. Post-intervention, overall objective cognition (p = 0.016), PCI (p = 0.004), fatigue (p = 0.011), and depression (p = 0.049) significantly improved. Post-intervention, high adherence was associated with significant improvements in PCI (p = 0.01) and fatigue (p = 0.03). High-intensity physical training was associated with significant improvements in PCI (p < 0.05), fatigue (p = 0.011) and depression (p = 0.037). Conclusions This intervention showed to be feasible and potentially efficient for the management of CRCI in patients with breast cancer. Trial registration NCT04213365, 27/12/2019.
There is a growing proportion of people with several disease conditions ("multimorbidity"), placing increasing demands on healthcare systems. One hypothesis is that clusters of diseases may arise from shared underlying disease processes (shared "pathogenesis"), whereby the presence of one disease indicates the state of disease progression to several related disease types. This article explains how this hypothesis can be tested using observational data for disease incidence. Specifically, a multistage model is used to test whether two diseases can have a "shared stage" or "step", before either disease can occur, and how the unobserved rate of this step can be determined. The approach offers a simple method for studying multiple diseases and identifying shared underlying causes of multiple conditions, and is illustrated with published data and numerical examples. The fundamental mathematical model is analysed to compare key statistical properties such as the expectation and variance with those of independent diseases. The main results do not need an understanding of the underlying mathematics and can be appreciated by a non-expert. Significance: It is widely believed that there are shared underlying pathways that can lead to several disease types (shared "pathogenesis"), and this may explain observed clusters of disease types. This article shows how this hypothesis can be tested for a pair or cluster of diseases, using observational data of disease incidence.
GM1 is one of the major glycosphingolipids (GSLs) on the cell surface in the central nervous system (CNS). Its expression level, distribution pattern, and lipid composition are dependent upon cell and tissue type, developmental stage, and disease state, which suggests a potentially broad spectrum of functions of GM1 in various neurological and neuropathological processes. The major focus of this review is the roles that GM1 plays in the development and activities of brains, such as cell differentiation, neuritogenesis, neuroregeneration, signal transducing, memory, and cognition, as well as the molecular basis and mechanisms for these functions. Overall, GM1 is protective for the CNS. Additionally, this review has also examined the relationships between GM1 and neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, GM1 gangliosidosis, Huntington’s disease, epilepsy and seizure, amyotrophic lateral sclerosis, depression, alcohol dependence, etc., and the functional roles and therapeutic applications of GM1 in these disorders. Finally, current obstacles that hinder more in-depth investigations and understanding of GM1 and the future directions in this field are discussed.
Dystonia is a neurodevelopmental disorder characterized by severe involuntary twisting movements, hypothesized to arise from a dysfunctional motor network involving the cortex, basal ganglia, and cerebellum. Within this network, striatal cholinergic interneurons have been identified as possible contributors to dystonia pathophysiology. However, little is known about striatal cholinergic interneuron development in the mammalian brain, limiting our understanding of its role in dystonia and therapeutic potential. Here, I review striatal cholinergic interneuron development in the context of early-onset DYT1 (or “DYT-TOR1A”) dystonia. I discuss clinical and laboratory research findings that support cholinergic dysfunction in DYT1 dystonia and the implications of abnormal cholinergic cell development on disease penetrance and striatal connectivity.
Neurology. Diseases of the nervous system, Diseases of the musculoskeletal system
This study presents the first implementation of multilayer neural networks on a memristor/CMOS integrated system on chip (SoC) to simultaneously detect multiple diseases. To overcome limitations in medical data, generative AI techniques are used to enhance the dataset, improving the classifier's robustness and diversity. The system achieves notable performance with low latency, high accuracy (91.82%), and energy efficiency, facilitated by end-to-end execution on a memristor-based SoC with ten 256x256 crossbar arrays and an integrated on-chip processor. This research showcases the transformative potential of memristive in-memory computing hardware in accelerating machine learning applications for medical diagnostics.
Shams Nafisa Ali, Afia Zahin, Samiul Based Shuvo
et al.
Cardiac auscultation, an integral tool in diagnosing cardiovascular diseases (CVDs), often relies on the subjective interpretation of clinicians, presenting a limitation in consistency and accuracy. Addressing this, we introduce the BUET Multi-disease Heart Sound (BMD-HS) dataset - a comprehensive and meticulously curated collection of heart sound recordings. This dataset, encompassing 864 recordings across five distinct classes of common heart sounds, represents a broad spectrum of valvular heart diseases, with a focus on diagnostically challenging cases. The standout feature of the BMD-HS dataset is its innovative multi-label annotation system, which captures a diverse range of diseases and unique disease states. This system significantly enhances the dataset's utility for developing advanced machine learning models in automated heart sound classification and diagnosis. By bridging the gap between traditional auscultation practices and contemporary data-driven diagnostic methods, the BMD-HS dataset is poised to revolutionize CVD diagnosis and management, providing an invaluable resource for the advancement of cardiac health research. The dataset is publicly available at this link: https://github.com/mHealthBuet/BMD-HS-Dataset.
Rare diseases affect millions worldwide but often face limited research focus due to their low prevalence. This results in prolonged diagnoses and a lack of approved therapies. Recent advancements in Large Language Models (LLMs) have shown promise in automating the extraction of medical information, offering potential to improve medical diagnosis and management. However, most LLMs lack professional medical knowledge, especially concerning rare diseases, and struggle to handle the latest rare disease information. They also cannot effectively manage rare disease data and are not directly suitable for diagnosis and management tasks. Our objective is to create an end-to-end system called AutoRD, which automates the extraction of information from medical texts about rare diseases, focusing on entities and their relations. AutoRD integrates up-to-date structured knowledge and demonstrates superior performance in rare disease extraction tasks. We conduct various experiments to evaluate AutoRD's performance, aiming to surpass common LLMs and traditional methods.
As a severe and highly contagious infectious disease, coronavirus disease 2019 (COVID-19) has caused a global pandemic. Several case reports have demonstrated that the respiratory system is the main target in patients with COVID-19, but the disease is not limited to the respiratory system. Case analysis indicated that the nervous system can be invaded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that 36.4% of COVID-19 patients had neurological symptoms. Importantly, the involvement of the CNS may be associated with poor prognosis and disease worsening. Here, we discussed the symptoms and evidence of nervous system involvement (directly and indirectly) caused by SARS-CoV-2 infection and possible mechanisms. CNS symptoms could be a potential indicator of poor prognosis; therefore, the prevention and treatment of CNS symptoms are also crucial for the recovery of COVID-19 patients.
Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID‐19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID‐19.
Thyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone level in the body can lead to nervous system-related problems linked to cognition, visual attention, visual processing, motor skills, language, and memory skills. TH has also been associated with neuropsychiatric disorders including schizophrenia, bipolar disorder, anxiety, and depression. Males and females display sex-specific differences in neuronal signaling. Steroid hormones including testosterone and estrogen are considered to be the prime regulators for programing the neuronal signaling in a male- and female-specific manner. However, other than steroid hormones, TH could also be one of the key signaling molecules to regulate different brain signaling in a male- and female-specific manner. Thyroid-related diseases and neurological diseases show sex-specific incidence; however, the molecular mechanisms behind this are not clear. Hence, it will be very beneficial to understand how TH acts in male and female brains and what are the critical genes and signaling networks. In this review, we have highlighted the role of TH in nervous system regulation and disease outcome and given special emphasis on its sex-specific role in male and female brains. A network model is also presented that provides critical information on TH-regulated genes, signaling, and disease.
Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.
M. Carmona-Abellan, R. Del Pino, A. Murueta-Goyena
et al.
Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity. Resumen: Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico.