关键词： AAV9   cisterna magna   gene therapy   neurological disorders  

关键词： Neurology   Outcomes research   Biomedicine   general   Neurosciences   Anatomy   Human Physiology   Neurochemistry   Neuropsychology  

摘要： Study design Retrospective review of ISNCSCI datasets. Objectives To discuss the correct classification of ISNCSCI datasets considered as challenging. Setting International expert collaboration. Methods The International Standards Committee of the American Spinal Injury Association (ASIA) receives challenging case scenarios regarding the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). Among those cases received, sample cases representing different categories of typical classification difficulties were identified by members of the International Standards committee. Results From the cases received, five sample cases were identified as representative for publication. These cases are related to the correct classification in the presence of non-SCI related conditions, the determination of motor zones of partial preservation in regions with no myotomes to test, the classification of the ASIA Impairment Scale in patients with substantial motor function below the motor level but no sacral sparing, the inclusion of non-key muscle functions in the classification of sensory incomplete individuals, and the correct classification of individuals with an amputation. Conclusion Presenting cases with challenging classifications, along with responses and explanations, will serve spinal cord injury professionals to better understand and utilize the ISNCSCI classification. As the ISNCSCI endorsed by ASIA and the International Spinal Cord Society (ISCoS) evolves over time, such resources are important to clarify inquiries from the spinal cord injury community and to understand the rationale for revisions.

关键词： MALDI IMS   Spatial distributions   Molecular map   Mass spectrometry   Brain disease   Neurology   Histology  

摘要： Neurological disease and disorders remain a large public health threat. Thus, research to improve early detection and/or develop more effective treatment approaches are necessary. Although there are many common techniques and imaging modalities utilized to study these diseases, existing approaches often require a label which can be costly and time consuming. Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is a label-free, innovative and emerging technique that produces 2D ion density maps representing the distribution of an analyte(s) across a tissue section in relation to tissue histopathology. One main advantage of MALDI IMS over other imaging modalities is its ability to determine the spatial distribution of hundreds of analytes within a single imaging run, without the need for a label or any a priori knowledge. Within the field of neurology and disease there have been several impactful studies in which MALDI IMS has been utilized to better understand the cellular pathology of the disease and or severity. Furthermore, MALDI IMS has made it possible to map specific classes of analytes to regions of the brain that otherwise may have been lost using more traditional methods. This review will highlight key studies that demonstrate the potential of this technology to elucidate previously unknown phenomenon in neurological disease.

关键词： Diseases of the nervous system   Spinal cord diseases   Biomedicine   general   Neurosciences   Anatomy   Human Physiology   Neurochemistry   Neuropsychology  

摘要： Study design Retrospective cohort study. Objectives To evaluate the effects of older age at the time of injury on the individuals' survival and neurological recovery within the first year after acute traumatic spinal cord injury (tSCI). Setting United States. Methods This study included all participants enrolled into the First National Acute Spinal Cord Injury Study (NASCIS-1). Outcome measures included survival and neurological recovery (as assessed using the NASCIS motor and sensory scores) within the first year after tSCI. Data analyses of neurological recovery were adjusted for major potential confounders. Results The study included 39 females and 267 males with overall mean age of 31 years who mostly sustained cervical severe tSCI after motor vehicle accidents or falls. Survival rates among older individuals are significantly lower than among younger individuals within the first year following tSCI (p < 0.0001). Among who survived the first year of tSCI, there were no statistically significant difference between older survivors and younger survivors regarding motor and sensory recovery in the multiple regression analyses adjusted for major potential confounders. Conclusions The results of this retrospective study suggest that older age at the injury onset is associated with lower survival rate within the first year following tSCI. However, older individuals have similar potential to recover from their initial neurological impairment to younger individuals after tSCI. The results of this study combined to the recent literature underline the need for multidisciplinary team approach to the management of the elderly with acute SCI is essential to maximize their recovery.

关键词： Cerebrovascular disease   Dilatative arteriopathy   MMP inhibition   Neurodegenerative diseases   Neuroprotection  

摘要： Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade the extracellular matrix and are responsible for many physiological and pathological processes. We aim to review the MMP inhibition from a clinical perspective and its possible therapeutic use in the future. MMPs play a role in various neurodegenerative and cerebrovascular diseases such as large artery atherosclerosis and ischemic stroke;for example, MMPs increase blood-brain barrier permeability favoring neuroinflammation. Synthetic MMPs inhibitors have been tested mostly in oncological trials and failed to demonstrate efficacy;some of them were discontinued because of the severe adverse reactions. Tetracyclines, in submicrobial doses, act as an MMP inhibitor, although tetracyclines have not yet been proven effective in several neurological conditions in which they were tested against placebo;it is uncertain whether there may be a use for tetracyclines in cerebrovascular disease, as a neuroprotective agent or in dolichoectasia.

关键词： Methodology   Behavioural neurology   Multiverse   Open science   Stroke  

摘要： Objective Multiverse analysis provides an ideal tool for understanding how inherent, yet ultimately arbitrary methodological choices impact the conclusions of individual studies. With this investigation, we aimed to demonstrate the utility of multiverse analysis for evaluating generalisability and identifying potential sources of bias within studies employing neurological populations. Methods Multiverse analysis was used to evaluate the robustness of the relationship between post-stroke visuospatial neglect and poor long-term recovery outcome within a sample of 1113 (age = 72.5, 45.1% female) stroke survivors. A total of 25,600 t-test comparisons were run across 400 different patient groups defined using various combinations of valid inclusion criteria based on lesion location, stroke type, assessment time, neglect impairment definition, and scoring criteria across 16 standardised outcome measures. Results Overall, 33.9% of conducted comparisons yielded significant results. 99.9% of these significant results fell below the null specification curve, indicating a highly robust relationship between neglect and poor recovery outcome. However, the strength of this effect was not constant across all comparison groups. Comparisons which included < 100 participants, pre-selected patients based on lesion type, or failed to account for allocentric neglect impairment were found to yield average effect sizes which differed substantially. Similarly, average effect sizes differed across various outcome measures with the strongest average effect in comparisons involving an activities of daily living measure and the weakest in comparisons employing a depression subscale. Conclusions This investigation demonstrates the utility of multiverse analysis techniques for evaluating effect robustness and identifying potential sources of bias within neurological research.

关键词： Neurological services   COVID-19   Neurology   Health services administration   Policies  

摘要： Background The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services. Methods A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November-December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February-April 2020, first pandemic wave, was also requested. Findings 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services' disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients' issues by their national government. Interpretation The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic

关键词： MDMA   Ecstasy   Cognition   Neurotoxicity   Memory   fMRI   PET   Substance use   Humans  

摘要： 3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons in primates, and reductions in markers of central serotonin axons, and axon terminals in animals. In humans, demonstration of serotonergic neurotoxicity is much more difficult to identify, and much of the research is complicated by confounding issues of polysubstance use, genetic and environmental factors and reliance on selfreports of previous drug use. We do not review the mechanisms for neurotoxicity in detail as they are covered elsewhere in this special issue. There is a large body of literature, however, which has investigated potential cognitive and neurocognitive consequences of repeated MDMA use. Here we review the literature on cognition, and neuroimaging studies that have investigated structural and functional brain changes associated with ecstasy use.

关键词： Out-of-hospital cardiac arrest   Biomarkers   Tau protein   Glial fibrillary acidic protein   Neurological outcome prognostication  

摘要： Aim: To determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: We measured plasma concentrations of GFAp and tau of patients included in the previously published COMACARE trial (NCT02698917) on intensive care unit admission and at 24, 48, and 72 h after OHCA, and compared them to neuron specific enolase (NSE). NSE concentrations were determined already during the original trial. We defined unfavourable outcome as a cerebral performance category (CPC) score of 3-5 six months after OHCA. We determined the prognostic accuracy of GFAp and tau using the receiver operating characteristic curve and area under the curve (AUROC). Results: Overall, 39/112 (35%) patients had unfavourable outcomes. Over time, both markers were evidently higher in the unfavourable outcome group (p < 0.001). At 48 h, the median (interquartile range) GFAp concentration was 1514 (886-4995) in the unfavourable versus 238 (135-463) pg/ ml in the favourable outcome group (p < 0.001). The corresponding tau concentrations were 99.6 (14.5-352) and 3.0 (2.2-4.8) pg/ml (p < 0.001). AUROCs at 48 and 72 h were 0.91 (95% confidence interval 0.85-0.97) and 0.91 (0.85-0.96) for GFAp and 0.93 (0.86-0.99) and 0.95 (0.89-1.00) for tau. Corresponding AUROCs for NSE were 0.86 (0.79-0.94) and 0.90 (0.82-0.97). The difference between the prognostic accuracies of GFAp or tau and NSE were not statistically significant. Conclusions: At 48 and 72 h, serum both GFAp and tau demonstrated excellent accuracy in predicting outcomes after OHCA but were not superior to NSE. Clinical trial registration: NCT02698917 (https://***/ct2/show/NCT02698917).

关键词： Ursodeoxycholic acid   Glycoursodeoxycholic acid   Tauroursodeoxycholic acid   Apoptosis   Oxidative stress   Inflammation  

摘要： Bile acids, mainly ursodeoxycholic acid (UDCA) and its conjugated species glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) have long been known to have anti-apoptotic, anti-oxidant and anti-inflammatory properties. Due to their beneficial actions, recent studies have started to investigate the effect of UDCA, GUDCA, TUDCA on the same mechanisms in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders, where increased cell apoptosis, oxidative stress and inflammation in the brain are often observed. A total of thirty-five pre-clinical studies were identified through PubMed/Medline, Web of Science, Embase, Psychlnfo, and CINAHL databases, investigating the role of the UDCA, GUDCA and TUDCA in the regulation of brain apoptosis, oxidative stress and inflammation, in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Findings show that UDCA reduces apoptosis, reactive oxygen species (ROS) and tumour necrosis factor (TNF)-alpha production in neurodegenerative models, and reduces nitric oxide (NO) and interleukin (IL)-1 beta production in neuropsychiatric models;GUDCA decreases lactate dehydrogenase, TNF-alpha and IL-1 beta production in neurological models, and also reduces cytochrome c peroxidase production in neurodegenerative models;TUDCA decreases apoptosis in neurological models, reduces ROS and IL-1 beta production in neurodegenerative models, and decreases apoptosis and TNF-alpha production, and increases glutathione production in neuropsychiatric models. In addition, findings suggest that all the three bile acids would be equally beneficial in models of Huntington's disease, whereas UDCA and TUDCA would be more beneficial in models of Parkinson's disease and Alzheimer's disease, while GUDCA in models of bilirubin encephalopathy and TUDCA in models of depression. Overall, this review confirms the therapeutic potential of UDCA, GUDCA and TUDCA in neurological, neurodegenerativ