Hasil untuk "Neurology. Diseases of the nervous system"

Zhihui Yang, Kevin K. W. Wang

I. Campbell, C. Abraham, E. Masliah et al.

A. Rana, A. Musto

Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn’s, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed. Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.

N. Ghasemi, S. Razavi, E. Nikzad

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe physical or cognitive disability as well as neurological defects. Although the etiology and pathogenesis of MS remains unclear, the present documents illustrate that the cause of MS is multifactorial and include genetic predisposition together with environmental factors such as exposure to infectious agents, vitamin deficiencies, and smoking. These agents are able to trigger a cascade of events in the immune system which lead to neuronal cell death accompanied by nerve demyelination and neuronal dysfunction. Conventional therapies for MS are based on the use of anti-inflammatory and immunomodulatory drugs, but these treatments are not able to stop the destruction of nerve tissue. Thus, other strategies such as stem cell transplantation have been proposed for the treatment of MS. Overall, it is important that neurologists be aware of current information regarding the pathogenesis, etiology, diagnostic criteria, and treatment of MS. Thus, this issue has been discussed according to recent available information.

C. Greene, N. Hanley, M. Campbell

Tight junction proteins of the blood–brain barrier are vital for maintaining integrity of endothelial cells lining brain blood vessels. The presence of these protein complexes in the space between endothelial cells creates a dynamic, highly regulated and restrictive microenvironment that is vital for neural homeostasis. By limiting paracellular diffusion of material between blood and brain, tight junction proteins provide a protective barrier preventing the passage of unwanted and potentially damaging material. Simultaneously, this protective barrier hinders the therapeutic effectiveness of central nervous system acting drugs with over 95% of small molecule therapeutics unable to bypass the blood–brain barrier. At the blood–brain barrier, claudin-5 is the most enriched tight junction protein and its dysfunction has been implicated in neurodegenerative disorders such as Alzheimer’s disease, neuroinflammatory disorders such as multiple sclerosis as well as psychiatric disorders including depression and schizophrenia. By regulating levels of claudin-5, it is possible to abrogate disease symptoms in many of these disorders. This review will give an overview of the blood–brain barrier and the role of tight junction complexes in maintaining blood–brain barrier integrity before focusing on the role of claudin-5 and its regulation in homeostatic and pathological conditions. We will also summarise therapeutic strategies to restore integrity of cerebral vessels by targeting tight junction protein complexes.

Sandro Dá Mesquita, A. Louveau, Andrea Vaccari et al.

H. Hagberg, P. Gressens, C. Mallard

Feizhi Song, Valerija Kovac, Behnam Mohammadi et al.

Raquel Martinez-Serra, Suji Lee, Igor Kraev et al.

Abstract Long-lasting synaptic changes enable memory storage and regulate recall in the brain. Our previous work established that generation of multi-innervated dendritic spines (MISs), spines with typically two excitatory presynaptic inputs, underlies hippocampal memory formation in aged, but not young mice. The identification of MIS generation was done by ultrastructural analysis in hippocampal CA1 stratum radiatum 24 h after contextual fear conditioning (CFC). However, our analysis did not consider multi-spine boutons (MSBs), which were recently shown to increase in complexity (complex MSBs are pre-synaptic boutons connecting with more than two post-synapses) at a later time point after CFC in young age. Therefore, we re-analyzed our three-dimensional electron microscopy images and show that, unexpectedly, MSB complexity, decreases in CA1 stratum radiatum 24 h after CFC. The decrease in MSB complexity occurred both in young and aged mice, indicating that aging has no impact on this synaptic change. Considering that complex MSBs link the activity of multiple postsynaptic neurons, we suggest that after CFC a decrease in MSB complexity may be required for specific memory recall.

P. Rodier, J. Ingram, Barbara Tisdale et al.

Hyun Lee, Eunjin Lee

Background Suicide is a serious social problem among older adults. However, little is known about how multidimensional factors affect suicide of older adults. Aims We classify the multidimensional suicidal risk types of older adults based on their characteristics and identify differences in suicidal ideation. Method Data were obtained via a nationwide online survey targeting 612 older adults over the age of 55 years. A latent profile analysis identified three profiles, one of which represented the optimal situation for these adults. Results We identified three distinct multidimensional suicidal risk types in older adults: high-risk predicament (24.5%), moderate-risk predicament (57.7%) and abundant internal/external resources (17.8%). In particular, depression, a major risk factor for suicide, was found together with self-neglect in each group. Multiple regression analysis showed that older adults in the moderate-risk predicament and high-risk predicament groups were more likely to have suicidal ideation than those in the abundant internal/external resources group. Conclusions Our findings suggest that co-occurrence of depression and self-neglect represents a suicide risk pattern in high-risk older individuals. Therefore, local communities need to urgently screen and provide interventions for such older adults and strengthen their capacity for multidimensional aspects of life to prevent suicide in the long term.

J. Na Bangxang, D. Sudjai, V. Arthayukti et al.

Introduction Substance use during pregnancy has become challenging clinical issue. Substance affects the brain, causing an addictive lifestyle. In pregnant women could lead more harm to neonatal life. Objectives This study investigates the neonatal outcome of substance use and associated factors. Methods A cross-sectional study was designed. Data were collected from pregnant women who used substance during labor and refer to rehabilitative consultation between 2017-2020. Neonate data were collected from perinatal care. Chi-square test and Fisher exact test were performed to analyze associated factors. A p-value less than 0.05 is considered significantly. Results 162 participants were included in this study. Mean age was 27.37±6.46 years. Mean age at first substance used was 21.93±6.52years. No antenatal care was found 45.7%. Methamphetamine was the most used during the first use (67.9%) and latest used (72.2%). Average birth weight was 2,734.97±617.51 gram. Gestational age at birth was 36.75±2.83 week. Average head circumference was 32.81±1.39 centimeters. Average femur length was 47.77±2.17 centimeters. Apgar score > 7 at 1 minute and 5 minute was found 94.4% and 97.2% . Neonatal complications were preterm labor (34.6%), low birth weight (25.3%), small for gestational age (19.8%), premature rupture of membranes (4.9%), and stillbirth (3.7%). No antenatal care (p=0.048), no antenatal care and birth before admission (p=0.023), a cesarean delivery (p=0.024), and gestational age more than 37 weeks (p<0.001) were associated with neonatal outcome in maternal with substance used during labor. Using amphetamine as the first substance related to neonatal complication (p=0.028). Conclusions Preterm labor, low birth weight and small gestational age are the most found as neonatal complications in maternal substance used during labor. No antenatal care was related with neonatal complications in this group. Therefore, an integrated system for the assessment of substances used in a pregnant woman and the system to reach out women who used substance and pregnant access to antenatal care should be established. Evaluation and rehabilitation are the interventions that should be done as soon as possible as primaray, secondary intervention. Disclosure of Interest None Declared

Ali Saadat, Jacques Fellay

Genetic diseases can be classified according to their modes of inheritance and their underlying molecular mechanisms. Autosomal dominant disorders often result from DNA variants that cause loss-of-function, gain-of-function, or dominant-negative effects, while autosomal recessive diseases are primarily linked to loss-of-function variants. In this study, we introduce a graph-of-graphs approach that leverages protein-protein interaction networks and high-resolution protein structures to predict the mode of inheritance of diseases caused by variants in autosomal genes, and to classify dominant-associated proteins based on their functional effect. Our approach integrates graph neural networks, structural interactomics and topological network features to provide proteome-wide predictions, thus offering a scalable method for understanding genetic disease mechanisms.

Elham Musaaed, Nabil Hewahi, Abdulla Alasaadi

In recent years, ML algorithms have been shown to be useful for predicting diseases based on health data and posed a potential application area for these algorithms such as modeling of diseases. The majority of these applications employ supervised rather than unsupervised ML algorithms. In addition, each year, the amount of data in medical science grows rapidly. Moreover, these data include clinical and Patient-Related Factors (PRF), such as height, weight, age, other physical characteristics, blood sugar, lipids, insulin, etc., all of which will change continually over time. Analysis of historical data can help identify disease risk factors and their interactions, which is useful for disease diagnosis and prediction. This wealth of valuable information in these data will help doctors diagnose accurately and people can become more aware of the risk factors and key indicators to act proactively. The purpose of this study is to use six supervised ML approaches to fill this gap by conducting a comprehensive experiment to investigate the correlation between PRF and Diabetes, Stroke, Heart Disease (HD), and Kidney Disease (KD). Moreover, it will investigate the link between Diabetes, Stroke, and KD and PRF with HD. Further, the research aims to compare and evaluate various ML algorithms for classifying diseases based on the PRF. Additionally, it aims to compare and evaluate ML algorithms for classifying HD based on PRF as well as Diabetes, Stroke, Asthma, Skin Cancer, and KD as attributes. Lastly, HD predictions will be provided through a Web-based application on the most accurate classifier, which allows the users to input their values and predict the output.

Vishwa Mohan, Chandrakanth Reddy Edamakanti, Vyom Sharma

Abstract Neurological disorders are characterized by progressive loss/damage of specific nerve cells due to accumulation of the disease-specific proteins. There is growing evidence that links neuronal damage with chronic activation of an innate immune response in the central nervous system. The immune system is inextricably involved in the brain development, but also regeneration and repair. This has stimulated therapeutic approaches to modulate the immune system in neurodegenerative diseases. Here, we discuss the current understanding of how astrocytes and microglia shape the neuroimmune responses to drive the pathology neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, polyglutamine (PolyQ) disorders, and the importance of inflammatory responses in the disease progression. There is common pattern of pathological events such as aggregating protein causes activation of microglia and astrocytes that in turn release proinflammatory factors that can be applied to several neurodegenerative disorders. In this context, the involvement of innate immunity seems to be a major paradigm in the pathogenesis of these diseases.

A. Erlangsen, E. Stenager, Y. Conwell et al.

Importance Neurological disorders have been linked to suicide, but the risk across a broad spectrum of neurological disorders remains to be assessed. Objectives To examine whether people with neurological disorders die by suicide more often than other people and to assess for temporal associations. Design, Setting, and Participants Nationwide, retrospective cohort study on all persons 15 years or older living in Denmark, from 1980 through 2016 (N = 7 300 395). Exposures Medical contact for head injury, stroke, epilepsy, polyneuropathy, diseases of myoneural junction, Parkinson disease, multiple sclerosis, central nervous system infections, meningitis, encephalitis, amyotrophic lateral sclerosis, Huntington disease, dementia, intellectual disability, and other brain diseases from 1977 through 2016 (n = 1 248 252). Main Outcomes and Measures Death by suicide during 1980-2016. Adjusted incidence rate ratio (IRRs) were estimated using Poisson regressions, adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and self-harm. Results Of the more than 7.3 million individuals observed over 161 935 233 person-years (49.1% males), 35 483 died by suicide (median duration of follow-up, 23.6 years; interquartile range, 10.0-37.0 years; mean age, 51.9 years; SD, 17.9 years). Of those, 77.4% were males, and 14.7% (n = 5141) were diagnosed with a neurological disorder, equivalent to a suicide rate of 44.0 per 100 000 person-years compared with 20.1 per 100 000 person-years among individuals not diagnosed with a neurological disorder. People diagnosed with a neurological disorder had an adjusted IRR of 1.8 (95% CI, 1.7-1.8) compared with those not diagnosed. The excess adjusted IRRs were 4.9 (95% CI, 3.5-6.9) for amyotrophic lateral sclerosis, 4.9 (95% CI, 3.1-7.7) for Huntington disease, 2.2 (95% CI, 1.9-2.6) for multiple sclerosis, 1.7 (95% CI, 1.6-1.7) for head injury, 1.3 (95% CI, 1.2-1.3) for stroke, and 1.7 (95% CI, 1.6-1.8) for epilepsy. The association varied according to time since diagnosis with an adjusted IRR for 1 to 3 months of 3.1 (95% CI, 2.7-3.6) and for 10 or more years, 1.5 (95% CI, 1.4 to 1.6, P < .001). Compared with those who were not diagnosed with a neurological disorder, those with dementia had a lower overall adjusted IRR of 0.8 (95% CI, 0.7-0.9), which was elevated during the first month after diagnosis to 3.0 (95% CI, 1.9-4.6; P < .001). The absolute risk of suicide for people with Huntington disease was 1.6% (95% CI, 1.0%-2.5%). Conclusions and Relevance In Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than persons not diagnosed with a neurological disorder. However, the absolute risk difference was small.

Laura M. Cox, H. Weiner

M. Schouler-Ocak

Abstract The code of ethics of the EPA intends to guide the ethical practice of psychiatry by offering a comprehensive approach to the ethical challenges in the field. It highlights universal ethical principles and considers their application to the specific practice of psychiatry. Ethical questions in psychiatric practice are manifold: tensions between respect for autonomy versus care and protection from harm, problems with coercive therapy and capacity for judgement etc. To receive more information, the Committee on Ethical Issues conducted a survey on “Ethics in psychiatric practice” to collect information from inpatient treatment settings of individual wards in psychiatric hospitals Europe-wide on following topics: - Experiences and practices addressing ethical conflicts and malpractice from the personal perspective of health care workers in these settings - Identification and engagement with violence - Measures for the reduction of restraints and coercion (violation of the autonomy of patients) In this talk, the preliminary results of this survey will be presented and discussed. Disclosure of Interest None Declared

Lorenzo Lorenzo-Luaces

Hui Jan Tan, Abdool Alleem Hj Shahren, Ching Soong Khoo et al.

IntroductionAnxiety has been increasingly recognized as part of the psychosocial health issues in COVID-19 patients. However, the impact of this topic may be underestimated in low- and middle-income countries. This study aimed to estimate the prevalence of and risk factors of anxiety in COVID-19 patients compared to controls in a local tertiary teaching hospital in Malaysia.MethodsIn this case–control study, we analyzed data on adult patients aged 18 years and above hospitalized for COVID-19 infection with matched hospitalized controls. The demographic, clinical data and anxiety measures using the Generalized Anxiety Disorder-7 questionnaire were analyzed using univariate and multivariate analysis.Results86.6% in the COVID-19 group had anxiety, significantly higher than 13.4% in the control group (p = 0.001). The COVID-19 group was significantly associated with the GAD-7 severity (p = 0.001). The number of COVID-19 patients in the mild, moderate, and severe anxiety groups was 48 (84.2%), 37 (86%), and 18 (94.7%), respectively. Multiple logistic regression showed significant predictors for anxiety, including COVID-19 diagnosis and neurological symptoms. Anxiety was found 36.92 times higher in the patients with COVID-19 compared to those without COVID-19 (OR 36.92;95% CI 17.09, 79.78, p = 0.001). Patients with neurological symptoms were at risk of having anxiety (OR 2.94; 95% CI 1.03, 8.41, p = 0.044).DiscussionCOVID-19 patients experience a significant disruption in psychosocial functioning due to hospitalization. The burden of anxiety is notably high, compounded by a diagnosis of COVID-19 itself and neurological symptomatology. Early psychiatric referrals are warranted for patients at risk of developing anxiety symptoms.