Hasil untuk "Neurology. Diseases of the nervous system"

A. Varatharaj, Ian Galea

The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how these changes may affect CNS function in health and disease. We first describe the structure and function of the BBB, and outline the techniques used to study the BBB in vitro, and in animal and human settings. We then summarise the evidence from a range of models linking BBB changes with systemic inflammation, and the underlying mechanisms. The clinical relevance of these BBB changes during systemic inflammation are discussed in the context of clinically-apparent syndromes such as sickness behaviour, delirium, and septic encephalopathy, as well as neurological conditions such as Alzheimer's disease and multiple sclerosis. We review emerging evidence for two novel concepts: (1) a heightened sensitivity of the diseased, versus healthy, BBB to systemic inflammation, and (2) the contribution of BBB changes induced by systemic inflammation to progression of the primary disease process.

L. Kalia, Anthony E. Lang

S. Hauser, B. Cree

Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative disease of the central nervous system, and the leading cause of non-traumatic neurological disability in young adults. Effective management requires a multifaceted approach to control acute attacks, manage progressive worsening, and remediate bothersome or disabling symptoms associated with this illness. Remarkable advances in treatment of all forms of MS, and especially for relapsing disease, have favorably changed the long-term outlook for many patients. There also has been a conceptual shift in understanding the immune pathology of MS, away from a purely T-cell-mediated model to recognition that B cells have a key role in pathogenesis. The emergence of higher-efficacy drugs requiring less frequent administration have made these preferred options in terms of tolerability and adherence. Many experts now recommend use of these as first-line treatment for many patients with early disease, before permanent disability is evident.

C. Baecher-Allan, B. Kaskow, H. Weiner

R. Verma, K. Vinoda, M. Papireddy et al.

Abstract Incineration of plastic waste in an open field is a major source of air pollution. Most of the times, the Municipal Solid Waste containing about 12% of plastics is burnt, releasing toxic gases like Dioxins, Furans, Mercury and Polychlorinated Biphenyls into the atmosphere. Further, burning of Poly Vinyl Chloride liberates hazardous halogens and pollutes air, the impact of which is climate change. The toxic substances thus released are posing a threat to vegetation, human and animal health and environment as a whole. Polystyrene is harmful to Central Nervous System. The hazardous brominated compounds act as carcinogens and mutagens. Dioxins settle on the crops and in our waterways where they eventually enter into our food and hence the body system. These Dioxins are the lethal persistent organic pollutants (POPs) and its worst component, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), commonly known as agentorange is a toxic compound which causes cancer and neurological damage, disrupts reproductive thyroid and respiratory systems. Thus, burning of plastic wastes increase the risk of heart disease, aggravates respiratory ailments such as asthma and emphysema and cause rashes, nausea or headaches, and damages the nervous system. Hence, a sustainable step towards tomorrow's cleaner and healthier environment needs immediate attention of the environmentalists and scientists. This review presents the hazards of incineration; open burning of plastics and effects of plastic in water and also a possibility of working out strategies to develop alternate procedures of plastic waste management.

M. Filippi, A. Bar-Or, F. Piehl et al.

B. Serafini, B. Rosicarelli, D. Franciotta et al.

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8+ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.

W. Poewe, E. Auff, F. Fazekas

K. Dineley, Anshul A. Pandya, J. Yakel

Nan Qiu, Benjamin Becker

The integration of artificial intelligence (AI) into mental health and psychiatry is transforming the diagnosis and treatment of mental disorders, including major depressive disorder (MDD). While the initial and promising applications span diagnostic screening and therapeutic chatbots, these first-wave technologies do not directly address brain changes or treat MDD. Noninvasive Brain Stimulation (NIBS) holds tremendous promise to address the biological heterogeneity of MDD, but is currently hindered by highly variable outcomes. Therefore, we posit that the synergistic integration of AI with NIBS represents the most promising path to address these difficulties. Importantly, the frontier for AI in depression treatment lies in a paradigm shift: from empirical trial-and-error to data-driven, personalized precision interventions. We argue for a paradigm shift away from AI roles in mental health (e.g., chatbots, diagnostics) toward its deep integration as the core engine for personalized, circuit-based neuromodulation. We highlight the key opportunities this fusion creates: identifying patient-specific neural targets through predictive modeling, developing adaptive closed-loop therapies, and leveraging brain digital twins for in silico simulation and protocol optimization. While significant challenges in data standardization, model interpretability, and clinical validation remain, the fusion of AI and NIBS heralds an era of psychiatry that is predictive, personalized, and precise.

Keisuke Ota, Hiroki Mani, Keita Nochimura et al.

BackgroundLateral trunk flexion (LTF) is a common symptom of Parkinson’s disease (PD). The sensory re-weighting system and sensory-motor function are poor in patients with PD and LTF, and this may cause gait impairment. However, the specific characteristics of gait impairment in patients with PD and LTF remain unclear. The aim of this study was to compare the characteristics of the gait functional domains between participants with PD with and without LTF.MethodsFifty-eight patients with PD and Hoehn–Yahr grade 2–3 LTF were divided into two groups: the LTF group (n = 22) and the No LTF group (n = 36). The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)-Part III score and subjective visual vertical (SVV) angle were measured. The participants walked with a motion sensor on a straight 20 m path at a comfortable speed. Fifteen gait variables (10 gait cycles) were evaluated and categorized into pace, rhythm, asymmetry, variability, and postural control functional domains and were compared between groups.ResultsThe LTF angle, SVV angle; MDS-UPDRS-Part III total, rigidity, and axial scores; and the coefficients of variance for step length, step time, and stance time were significantly higher in the LTF group than in the No LTF group. No other significant differences were observed between the groups.ConclusionParticipants with PD and Hoehn–Yahr severity 2–3 LTF had greater gait variability than those without LTF, but maintained similar pace, rhythm, asymmetry, and postural control domains. Patients with PD and LTF may develop abnormal neural networks causing greater gait variability.

Alexandra Hochstetler, Christine Hehnly, William Dawes et al.

Abstract The Hydrocephalus Association organized two workshops with the support of the Rudi Schulte Research Institute and Cincinnati Children's Hospital Medical Center entitled “Developing Non-Invasive Hydrocephalus Therapies: Molecular and Cellular Targets”, held September 27–29, 2023, in Dallas, TX, and “Developing Non-Invasive Hydrocephalus Therapies: Advancing Towards Clinical Trials”, held April 12–13, 2024, in Cincinnati, OH. The goal of these workshops was to explore the frontiers of ongoing research for non-invasive therapies for the treatment of hydrocephalus across all etiologies and to improve patient outcomes at all stages of diagnosis and management. During the consensus-building discussions throughout the research workshops, basic, translational, and clinical scientists aimed to identify the next steps to develop novel treatments for hydrocephalus. This detailed report discusses the research priorities that emerged from these workshops to inspire researchers and guide studies towards better treatment for people living with hydrocephalus.

Abduz Zami, Shadman Sobhan, Rounaq Hossain et al.

Image segmentation plays a vital role in the medical field by isolating organs or regions of interest from surrounding areas. Traditionally, segmentation models are trained on a specific organ or a disease, limiting their ability to handle other organs and diseases. At present, few advanced models can perform multi-organ or multi-disease segmentation, offering greater flexibility. Also, recently, prompt-based image segmentation has gained attention as a more flexible approach. It allows models to segment areas based on user-provided prompts. Despite these advances, there has been no dedicated work on prompt-based interactive multi-organ and multi-disease segmentation, especially for Chest X-rays. This work presents two main contributions: first, generating doodle prompts by medical experts of a collection of datasets from multiple sources with 23 classes, including 6 organs and 17 diseases, specifically designed for prompt-based Chest X-ray segmentation. Second, we introduce Prompt2SegCXR, a lightweight model for accurately segmenting multiple organs and diseases from Chest X-rays. The model incorporates multi-stage feature fusion, enabling it to combine features from various network layers for better spatial and semantic understanding, enhancing segmentation accuracy. Compared to existing pre-trained models for prompt-based image segmentation, our model scores well, providing a reliable solution for segmenting Chest X-rays based on user prompts.

A. Ramesh, Ryan D. Schubert, Ariele L. Greenfield et al.

Significance B cells serve as a key weapon against infectious diseases. They also contribute to multiple autoimmune diseases, including multiple sclerosis (MS) where depletion of B cells is a highly effective therapy. We describe a comprehensive profile of central nervous system (CNS)-specific transcriptional B cell phenotypes in MS at single-cell resolution with paired immune repertoires. We reveal a polyclonal immunoglobulin M (IgM) and IgG1 cerebrospinal fluid B cell expansion polarized toward an inflammatory, memory and plasmablast/plasma cell phenotype, with differential up-regulation of specific proinflammatory pathways. We did not find evidence that CNS B cells harbor a neurotropic virus. These data support the targeting of activated resident B cells in the CNS as a potentially effective strategy for control of treatment-resistant chronic disease. Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-κB) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-β1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood–brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein–Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.

S. Grant, S. DeMorrow

Bile acids are commonly known as digestive agents for lipids. The mechanisms of bile acids in the gastrointestinal track during normal physiological conditions as well as hepatic and cholestatic diseases have been well studied. Bile acids additionally serve as ligands for signaling molecules such as nuclear receptor Farnesoid X receptor and membrane-bound receptors, Takeda G-protein-coupled bile acid receptor and sphingosine-1-phosphate receptor 2. Recent studies have shown that bile acid signaling may also have a prevalent role in the central nervous system. Some bile acids, such as tauroursodeoxycholic acid and ursodeoxycholic acid, have shown neuroprotective potential in experimental animal models and clinical studies of many neurological conditions. Alterations in bile acid metabolism have been discovered as potential biomarkers for prognosis tools as well as the expression of various bile acid receptors in multiple neurological ailments. This review explores the findings of recent studies highlighting bile acid-mediated therapies and bile acid-mediated signaling and the roles they play in neurodegenerative and neurological diseases.

Dandan Wan, Tingfu Du, Weiqi Hong et al.

Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.

Maryam Shafaati, M. Zandi

Viral infectious diseases have various neurological manifestations, whether they are epidemic or pandemic in nature. Nonspecific encephalopathy is the most common central nervous system (CNS) manifestation. The spectrum of nervous evidence varies for viral pathogens. Some infectious viruses, such as the Ebola virus, exhibit direct neurotropism. Others, such as the Rift Valley fever virus, have the potential for neurotropism. Direct neurotropism is unknown in monkeypox virus, SARS-CoV-2, MERS-CoV, and even smallpox. As seen in the COVID-19, there may be evidence of para-infectious neurological syndrome. There have only been a few reports of neurological diseases caused by monkeypox infection. Future efforts to prevent the spread of infectious disease surges can reduce mortality complications, the therapeutic burden on the health-care system, and prevent further spread. This study describes the clinical and neurological complications of monkeypox infection, particularly encephalitis, as well as the laboratory diagnosis of these cases.

Jinping Cheng, Nils Korte, R. Nortley et al.

Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood–brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood–brain barrier, capillary blood flow and the movement of immune cells into the brain. They also form part of the “glial” scar isolating damaged parts of the CNS, and may have stem cell-like properties. Recent studies have suggested that pericytes play a crucial role in neurological diseases, and are thus a therapeutic target in disorders as diverse as stroke, traumatic brain injury, migraine, epilepsy, spinal cord injury, diabetes, Huntington’s disease, Alzheimer’s disease, diabetes, multiple sclerosis, glioma, radiation necrosis and amyotrophic lateral sclerosis. Here we report recent advances in our understanding of pericyte biology and discuss how pericytes could be targeted to develop novel therapeutic approaches to neurological disorders, by increasing blood flow, preserving blood–brain barrier function, regulating immune cell entry to the CNS, and modulating formation of blood vessels in, and the glial scar around, damaged regions.

Cheng Xie, Dongling Zhong, Yue Zhang et al.

BackgroundCognitive impairment is prevalent in Chinese patients with hypertension; however, current evidence on prevalence and risk factors is required to be synthesized.ObjectivesThis systematic review and meta-analysis aimed to evaluate the prevalence and risk factors of cognitive impairment in Chinese patients with hypertension.MethodsTwo reviewers independently searched PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, the Wanfang database, and the VIP database from their inception to 7 June 2023. The gray literature and the reference lists of the included studies were also retrieved manually. Moreover, we also independently performed the eligibility screening, data extraction, and data synthesis. The primary outcome was the prevalence of cognitive impairment in Chinese patients with hypertension, and the secondary outcomes were the risk factors for cognitive impairment in patients with hypertension. R (version 4.0.3) was used for data synthesis.ResultsIn total, 82 studies involving 53,623 patients with hypertension were included in this meta-analysis. The pooled prevalence of cognitive impairment in patients with hypertension was 37.6% (95% CI: 33.2–42.2%). A total of 12 risk factors, including advanced age (r = −0.34, 95% CI: −0.45, −0.21), female sex (OR = 1.15, 95% CI: 1.01–1.32), BMI > 24 Kg/m2 (OR = 1.76, 95% CI: 1.04–3.00), lower educational level (OR = 2.01, 95% CI: 1.10–3.67), single status (OR = 1.63, 95% CI: 1.32–2.02), complications with diabetes (OR = 1.44, 95% CI: 1.14–1.80), coronary heart disease (OR = 1.49, 95% CI: 1.12–1.97), higher stage of hypertension [stage 3 vs. stage 1, OR = 3.08, 95% CI: 1.82–5.22; stage 2 vs. stage 1, OR = 1.83, 95% CI: 1.29–2.60], no regular physical activity (OR = 0.40, 95% CI: 0.21–0.77), higher levels of systolic blood pressure (r = −0.25, 95% CI: −0.42, −0.08), Hcy (r = −0.39, 95% CI: −0.63, −0.09), and IL-6 (r = −0.26, 95% CI: −0.48, −0.02) were detected.ConclusionCognitive impairment is prevalent in Chinese patients with hypertension, and the increased prevalence was associated with several demographic characteristics, complicated disease, no regular physical activity, worse hypertension status (higher stages and SBP), and high levels of biomarkers. Therefore, more attention should be paid to the early identification and treatment of patients with hypertension who are at high risk for cognitive impairment in clinical practice. In addition, relevant risk factors should be controlled to reduce the incidence of cognitive impairment.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier [CRD42023410437].

Elisa dePaula França Resende, Vivian P. Lara, Ana Luisa C. Santiago et al.

Abstract INTRODUCTION The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. METHODS Thirty‐five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults [TOFHLA]), structural and resting state functional magnetic resonance imaging, and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score < 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. RESULTS Participants were mostly female (57.1%) and self‐declared as being Black individuals (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0; 42.5] out of 100 points and the median free recall score was 30.0 [26.2; 35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm3. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. The right hippocampal connectivity positively correlated with the literacy scores (β = 0.58, P = 0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. DISCUSSION Low literacy levels correlated with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in this sample. Highlights A significant link was found between health literacy and hippocampal connectivity. Enhanced hippocampus– ventromedial prefrontal cortex connectivity suggests potential cognitive reserve improvement. Higher cognitive reserve may protect against hippocampal atrophy and neurodegeneration. Health literacy improvements could help prevent cognitive impairment in illiterate populations. Study highlights importance of considering structural racism in brain connectivity research.