Hasil untuk "Neurology. Diseases of the nervous system"

M. Eddleston, L. Mucke

The central nervous system responds to diverse neurologic injuries with a vigorous activation of astrocytes. While this phenomenon is found in many different species, its function is obscure. Understanding the molecular profile characteristic of reactive astrocytes should help define their function. The purpose of this review is to provide a summary of molecules whose levels of expression differentiate activated from resting astrocytes and to use the molecular profile of reactive astrocytes as the basis for speculations on the functions of these cells. At present, reactive astrocytosis is defined primarily as an increase in the number and size of cells expressing glial fibrillary acidic protein. In vivo, this increase in glial fibrillary acidic protein-positive cells reflects predominantly phenotypic changes of resident astroglia rather than migration or proliferation of such cells. Upon activation, astrocytes upmodulate the expression of a large number of molecules. From this molecular profile it becomes apparent that reactive astrocytes may benefit the injured nervous system by participating in diverse biological processes. For example, upregulation of proteases and protease inhibitors could help remodel the extracellular matrix, regulate the concentration of different proteins in the neuropil and clear up debris from degenerating cells. Cytokines are key mediators of immunity and inflammation and could play a critical role in the regulation of the blood-central nervous system interface. Neurotrophic factors, transporter molecules and enzymes involved in the metabolism of excitotoxic amino acids or in the antioxidant pathway may help protect neurons and other brain cells by controlling neurotoxin levels and contributing to homeostasis within the central nervous system. Therefore, an impairment of astroglial performance has the potential to exacerbate neuronal dysfunction. Based on the synopsis of studies presented, a number of issues become apparent that deserve a more extensive analysis. Among them are the relative contribution of microglia and astrocytes to early wound repair, the characterization of astroglial subpopulations, the specificity of the astroglial response in different diseases as well as the analysis of reactive astrocytes with techniques that can resolve fast physiologic processes. Differences between reactive astrocytes in vivo and primary astrocytes in culture are discussed and underline the need for the development and exploitation of models that will allow the analysis of reactive astrocytes in the intact organism.

L. Galland

D. Gilden, B. Kleinschmidt-DeMasters, James J. Laguardia et al.

M. Sharief, R. Hentges

V. Feigin, A. Abajobir, K. H. Abate et al.

Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.

J. Verhaagen, J. David Mcdonald

Gaurav Nepal, J. Rehrig, G. Shrestha et al.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. Methods Any study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. Results Our systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell’s palsy, and skeletal muscle manifestations such as rhabdomyolysis. Conclusion While COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.

Sujit Sarkhel, Sandeep Grover

Morteza Abyadeh, Vivek Gupta, Yuyi You et al.

Konstantin Kohlhase, Ferdinand O. Bohmann, Christian Grefkes et al.

Abstract Background Advances in secondary stroke prevention, including direct oral anticoagulants (DOACs), dual antiplatelet therapies (DAPT), and cardiovascular risk management, have changed costs over the past decade. This study aimed to evaluate annual treatment costs and trends in drug-based secondary prophylaxis after ischemic strokes. Methods Annual treatment costs were evaluated using the net costs per defined daily dosage (DDD) of discharge medications for ischemic stroke patients treated in 2020 at the University Hospital Frankfurt, Germany. Evaluated drugs included acetylsalicylic acid, adenosine diphosphate inhibitors, DOACs, vitamin K antagonists, lipid-lowering drugs (LLD), antihypertensives (AHT), and oral antidiabetics (OD). Kruskal–Wallis test examined intergroup differences in substance groups and stroke etiologies. DDD development between 2004 and 2021 was further evaluated for significant trend changes using an interrupted time series analysis. Results The study included 422 patients (70.5 ± 12.9 years, 43.1% female). Etiologies divided into large-artery atherosclerosis (29.9%), cardioembolic (25.6%), cryptogenic (26.8%), and small-vessel disease (17.8%). The total estimated annual drug expenditure was € 241,808; of which 51.6% was due to DOACs (median € 1157 [Q1–Q3:1157–1157], p < 0.006), 20.0% to AHTs (€127.8 [76.7–189.8]), 15.7% to ODs (€525.6 [76.7–641.5]), and 8.7% to LLDs (€43.8 [43.8–43.8]). Cardioembolic strokes had the highest annual costs per patient (€1328.6 [1169.0–1403.4]) with higher expenditure for DOACs (p < 0.001) and AHTs (p < 0.026). DAPT costs were highest for large-vessel strokes (p < 0.001) and accounted for 2.5% of total costs. There was a significant trend change in DDDs for clopidogrel in 2010 (p < 0.001), for prasugrel in 2017 (p < 0.001), for ASA in 2015 (p < 0.001) and for DOACs in 2012 (p = 0.017). Conclusions DOACs for cardioembolic strokes were the primary cost driver in drug-based secondary stroke prevention, whereas permanent ASA and DAPT only accounted for a minor cost proportion. LLDs were associated with lower costs than AHTs and ODs. There were significant changes in DDDs for the respective substances, whereas the costs for DOACs as the most expensive pharmaceuticals remained widely stable across the last decade.

Kyle H. Flippo, S. Strack

Kanthee Anantapong, Helena Ferreira Moura, Pichet Udomratn et al.

Geopsychiatry, a newly emerging discipline within psychiatry, examines the influence of geopolitical determinants on mental health and mental illness. Geopolitical determinants include conflict and wars, global austerity, climate change, public health crises (such as the coronavirus disease 2019 (COVID-19)), and migration. This study focuses on the two significant areas of climate change and migration. Climate change can affect mental health directly or indirectly in a variety of ways, including chronic (global warming) and acute (heat waves and environmental disasters) events. Certain groups of migrants, including migrating children, older migrants, refugees, and asylum seekers, are particularly vulnerable to developing psychiatric disorders. The convergence of climate change and migration is significantly complicating the already highly difficult situation for mental health services worldwide, particularly in low- and middle-income countries where access to care is limited. Despite this, the majority of studies examining mental health impacts of these events originate from high-income countries, and there is still a lack of effective preventive and treatment strategies. In 2023, the World Psychiatric Association (WPA) set up a Special Interest Group on Geopsychiatry with a clear and explicit aim to summarize current evidence and propose strategies to tackle geopolitical challenges on mental health. The Special Interest Group aims to support regional and local groups across all psychiatric disciplines and stakeholders dedicated to building local consensus, prioritizing research, crafting policies, and collating and sharing good clinical practices. With such significant effort, we can expand our understanding and collaboration on geopsychiatry and make changes to the care of people with geopolitical and mental health challenges around the globe.

宋金云，赵宏宇 (SONG Jinyun, ZHAO Hongyu )

目的 采用两样本双向孟德尔随机化（Mendelian randomization，MR）方法分析慢性肾病（chronic kidney disease，CKD）与卒中之间的因果关系。 方法 正向研究以CKD为暴露因素，卒中为结局变量，获取CKD和卒中的全基因组关联分析数据，筛选出与CKD显著相关的单核苷酸多态性（single nucleotide polymorphism，SNP）作为工具变量。反向研究则筛选与卒中密切相关的SNP作为工具变量，CKD作为结局变量。使用逆方差加权法、加权中位数法和MR-Egger回归法进行双向MR分析，探讨CKD与卒中的因果关系。通过Cochran’s Q检验评估异质性，MR-Egger回归截距项进行多效性检验以及留一法进行敏感性分析，以评估MR结果的稳健性。 结果 正向研究共获得4个与CKD显著相关的SNP作为最终的工具变量，逆方差加权法结果显示CKD与卒中之间具有显著的正向因果关系（OR 1.123，95%CI 1.051～1.200，P＜0.001）。反向MR结果显示，卒中也会增加CKD的发生风险（OR 1.213，95%CI 1.003～1.466，P=0.046）。未发现异质性和水平多效性（均P>0.05），逐个剔除SNP后，MR分析结果稳健。 结论 CKD与卒中存在双向因果关系，CKD会增加卒中的风险，而卒中也会增加CKD的发生风险。 Abstract: Objective Two-sample bidirectional Mendelian randomization (MR) method was used to analyze the causality between chronic kidney disease (CKD) and stroke. Methods With CKD as the exposure factor and stroke as the outcome variable, the forward study obtained the genome-wide association study data for CKD and stroke, and screened out the single nucleotide polymorphisms (SNPs) significantly associated with CKD as instrumental variables. The reverse study screened SNPs closely related to stroke as instrumental variables, with CKD as the outcome variable. Inverse variance weighted, weighted median, and MR-Egger regression were used for bidirectional MR analysis to explore the causality between CKD and stroke. Heterogeneity was evaluated using Cochran’s Q test, pleiotropy was tested using the intercept term of MR-Egger regression, and sensitivity analysis was performed using the leave-one-out to evaluate the robustness of the MR results. Results In the forward study, four SNPs significantly correlated with CKD were obtained as the final instrumental variables, and the results of inverse variance weighted showed a significant positive causality between CKD and stroke (OR 1.123, 95%CI 1.051-1.200, P＜0.001). Reverse MR results showed that stroke also increased the risk of CKD (OR 1.213, 95%CI 1.003-1.466, P=0.046). No heterogeneity or horizontal pleiotropy was found (both P>0.05) , and the results of MR analysis were robust after removing SNPs one by one. Conclusions Bidirectional causality was observed between CKD and stroke. CKD increases the risk of stroke, and stroke also increases the risk of CKD.

Dilek Örüm, Mehmet Hamdi Örüm, Yaşar Kapıcı et al.

Abstract Background Methamphetamine use and related direct and indirect problems are increasing all over the world. The coexistence of lifetime marijuana use (LMU) and methamphetamine use disorder (MUD) may also be accompanied by psychotic symptoms (MAP). Methamphetamine and marijuana use are known to pose risks for cardiovascular diseases (CVDs). However, ten-year CVD risk and inflammation markers of LMU-MUD (non-psychosis group) and LMU-MAP (psychosis group) subjects and the relationship of various sociodemographic and clinical variables with these markers have not yet been examined. Methods Thirty-two male subjects were included in non-psychosis group and 72 male subjects in psychosis group. Sociodemographic and clinical characteristics were recorded. Psychotic symptom severity of psychosis group subjects was measured. The ten-year CVD risk was calculated using QRISK®3 model. Results Age, cigarettes/pack-years, alcohol use onset age, drug use onset age, methamphetamine use onset age, duration of methamphetamine use, education and marital status of the groups were similar (p > 0.05). There was a statistical difference between the non-psychosis and psychosis groups in terms of self-mutilation history (p < 0.001), suicidal attempt history (p = 0.007), homicidal attempt history (p = 0.002), psychiatric hospitalization history (p = 0.010). Ten-year QRISK®3 score was 4.90 ± 9.30 in the psychosis group, while it was 1.60 ± 1.43 in the non-psychosis group (p = 0.004). The mean heart age of the psychosis group was 14 years higher than their chronological age, while the mean heart age of the non-psychosis group was 8 years higher. Neutrophil to lymphocyte ratio (NLR) (p = 0.003) was higher in the psychosis group. A significant correlation was detected between ten-year QRISK®3 and positive psychotic symptoms in the psychosis group (r = 0.274, p = 0.020). Regression analysis showed that self-mutilation history, NLR and relative risk obtained from QRISK®3 can be used to distinguish non-psychosis group and psychosis group subjects (sensitivity = 91.7; Nagelkerke R2 0.438; p = 0.001). Conclusions This study is important as it demonstrates for the first time that among the subjects using marijuana and methamphetamine, those with psychotic symptoms have a higher NLR and ten-year CVD risk.

Yi Zhou, Xiaomei Jin, Xiaorong Liu et al.

PurposeTo explore the relationship between obstructive sleep apnea (OSA) and hypoperfusion during ultra-early acute cerebral infarction.Patients and methodsData were retrospectively collected from patients admitted to our hospital with acute cerebral infarction between January 2020 and January 2022, who underwent comprehensive whole-brain computed tomography perfusion imaging and angiography examinations within 6 h of onset. The F-stroke software automatically assessed and obtained relevant data (Tmax). The patients underwent an initial screening for sleep apnea. Based on their Apnea-Hypopnea Index (AHI), patients were categorized into an AHI ≤15 (n = 22) or AHI &gt;15 (n = 25) group. The pairwise difference of the time-to-maximum of the residue function (Tmax) &gt; 6 s volume was compared, and the correlation between AHI, mean pulse oxygen saturation (SpO2), oxygen desaturation index (ODI), percentage of time with oxygen saturation &lt; 90% (T90%), and the Tmax &gt;6 s volume was analyzed.ResultsThe Tmax &gt;6 s volume in the AHI &gt; 15 group was significantly larger than that in the AHI ≤ 15 group [109 (62–157) vs. 59 (21–106) mL, p = 0.013]. Spearman’s correlation analysis revealed Tmax &gt;6 s volume was significantly correlated with AHI, mean SpO2, ODI, and T90% in the AHI &gt; 15 group, however, no significant correlations were observed in the AHI ≤ 15 group. Controlling for the site of occlusion and Multiphase CT angiography (mCTA) score, AHI (β = 0.919, p &lt; 0.001), mean SpO2 (β = −0.460, p = 0.031), ODI (β = 0.467, p = 0.032), and T90% (β =0.478, p = 0.026) remained associated with early hypoperfusion in the AHI &gt; 15 group.ConclusionIn patients with acute cerebral infarction and AHI &gt; 15, AHI, mean SpO2, ODI and T90% were associated with early hypoperfusion. However, no such relationship exists among patients with AHI ≤ 15.

Chuncao Ao, Chenchen Li, Jing Chen et al.

Neurological disorders are a group of disorders with motor, sensory or cognitive damage, caused by dysfunction of the central or peripheral nervous system. Cyclin-dependent kinases 5 (Cdk5) is of vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration. However, when the nervous system is subject to pathological stimulation, aberrant activation of Cdk5 will induce abnormal phosphorylation of a variety of substrates, resulting in a cascade signaling pathway, and thus lead to pathological changes. Cdk5 is intimately related to the pathological mechanism of a variety of neurological disorders, such as A-β protein formation in Alzheimer’s disease, mitochondrial fragmentation in cerebral ischemia, and apoptosis of dopaminergic neurons in Parkinson’s disease. It is worth noting that Cdk5 inhibitors have been reported to have neuroprotective effects by inhibiting related pathological processes. Therefore, in this review, we will briefly introduce the physiological and pathological mechanisms of Cdk5 in the nervous system, focusing on the recent advances of Cdk5 in neurological disorders and the prospect of targeted Cdk5 for the treatment of neurological disorders.

Mariëlle M. C. van der Hoorn, Gerard A. Kalkman, Yvette M. Weesie et al.

Background Chronic high-dose (CHD) prescription opioid use is a major public health concern. Although CHD opioid use has been associated with psychiatric disorders, the causality could go both ways. Some studies have already linked psychiatric disorders to an increased risk of transitioning to chronic opioid use, and longitudinal data identifying psychiatric disorders as predictors of CHD opioid use could shed further light on this issue. Aims To prospectively examine the relationship between the presence of a psychiatric disorder and subsequent development of CHD opioid use in primary care patients newly receiving opioids. Method Data were included from 137 778 primary care patients in The Netherlands. Cox regression modelling was used to examine the association between psychiatric disorders prior to a new opioid prescription and subsequent CHD opioid use (≥90 days; ≥50 mg/day oral morphine equivalents) in the subsequent 2 years. Results Of all patients receiving a new opioid prescription, 2.0% developed CHD opioid use. A psychiatric disorder before the start of an opioid prescription increased the risk of CHD opioid use (adjusted hazard ratio HR = 1.74; 95% CI 1.62–1.88), specifically psychotic disorders, substance use disorders, neurocognitive disorders and multiple co-occurring psychiatric episodes. Similarly, pharmacotherapy for psychosis, substance use disorders and mood and/or anxiety disorders increased the risk of CHD opioid use. Psychiatric polypharmacy conferred the greatest risk of developing CHD opioid use. Conclusions Psychiatric disorders increase the risk of developing CHD opioid use in patients newly receiving prescription opioids. To reduce the public health burden of CHD opioid use, careful monitoring and optimal treatment of psychiatric conditions are advised when opioid therapy is initiated.

F. Masini, G. Caramanico, G. Menculini et al.

Introduction The COVID-19 outbreak and the related containment measures led to the emergence of psychological distress in youth populations, possibly due to concern for their families, social isolation, increased time spent on the Internet and social media, and anxiety about the future. Objectives The study aims to evaluate differences in the access of children, adolescents, and young adults to a psychiatric emergency setting before and after the onset of the COVID-19 pandemic. Methods Data concerning the psychiatric consultations carried out at the Emergency Department of the University Hospital of Perugia was collected. Socio-demographic and clinical information, including diagnostic and treatment features, was entered into an electronic database. We considered two different time spans, one before (01.06.2017-31.12.2018) and one after (01.06.2020-31.12.2021) the COVID-19 pandemic outbreak. The characteristics of consultations carried out before and after the pandemic outbreak were compared by means of bivariate analyses (p<0.05). Results 2,457 psychiatric consultations were carried out in the index periods. 1,319 (53.7%) were requested before, while 1,138 (46.3%) after the COVID-19 outbreak. As for the latter, these were more frequently requested for female subjects (64.2% vs 54.5%, p=0.0042), while institutionalized people underwent psychiatric consultations less frequently in the post-COVID-19 period (5.6% vs 18.2% p<0.001). A significant difference in the prevalence of anxiety disorders (9.7% post-COVID-19 vs 18.8% pre-COVID-19, p=0.009) and adjustment disorders was found (7.1% vs 1.5%, p=0.009). Substance-related disorders were significantly reduced (8.0% vs 15.8%, p=0.016) after the COVID-19 outbreak. About psychopharmacological treatment, there was an increase in people who had received treatment in the past but were no longer on treatment (52.3% vs 30.8%, p<0.001). The prescription of antipsychotics also increased (29.3% vs 18.5%, p=0.012). At discharge, subjects were more frequently hospitalized in the Psychiatric Inpatient Unit in the post-COVID-19 period (22.2% vs 12.8%, p=0.012). Conclusions Our data confirms the vulnerability of youth populations during the pandemic. The consequences of health emergencies on the psychological well-being of this population must not be underestimated and tailored treatment strategies should be implemented. Disclosure of Interest None Declared

A. Minagar, P. Shapshak, R. Fujimura et al.

Katherine S.F. Damme, Jadyn S. Park, Teresa Vargas et al.

Background: Motor abnormalities, such as psychomotor agitation and retardation, are widely recognized as core features of depression. However, it is not currently known whether motor abnormalities connote risk for depression. Methods: Using data from the Adolescent Brain Cognitive Development (ABCD) Study, a nationally representative sample of youth (N = 10,835, 9–11 years old), the present paper examines whether motor abnormalities are associated with 1) depression symptoms in early adolescence, 2) familial risk for depression (familial risk loading), and 3) future depression symptoms. Motor abnormality measures included traditional (DSM) motor signs such as psychomotor agitation and retardation as well as other motor domains such as developmental motor delays and dyscoordination. Results: Traditional motor abnormalities were less prevalent (agitation = 3.2%, retardation = 0.3%) than nontraditional domains (delays = 13.79%, coordination = 35.5%) among adolescents. Motor dysfunction was associated with depression symptoms (Cohen’s d = 0.02 to 0.12). Familial risk for depression was related to motor abnormalities (Cohen’s d = 0.08 to 0.27), with the exception of motor retardation. Family vulnerability varied in sensitivity to depression risk (e.g., retardation: 0.53%; dyscoordination: 32.05%). Baseline endorsement of motor abnormalities predicted future depression symptoms at 1-year follow-up. Conclusions: These findings suggest that motor signs reflect a novel, promising future direction for examining vulnerability to depression risk in early adolescence.