关键词： Acute and chronic phases   blood-brain barrier leakage   contact system   Fasciola excretome   secretome   fibrinolysis system   human fascioliasis   indicators and prevention   neurological disorders   plasminogen-binding proteins   proteomic and mass spectrometry analyses  

摘要： Human fascioliasis is a worldwide, pathogenic food-borne trematodiasis. Impressive clinical pictures comprising puzzling polymorphisms, manifestation multifocality, disease evolution changes, sequelae and mortality, have been reported in patients presenting with neurological, meningeal, neuropsychic and ocular disorders caused at distance by flukes infecting the liver. Proteomic and mass spectrometry analyses of the Fasciola hepatica excretome/secretome identified numerous, several new, plasminogen-binding proteins enhancing plasmin generation. This may underlie blood-brain barrier leakage whether by many simultaneously migrating, small-sized juvenile flukes in the acute phase, or by breakage of encapsulating formations triggered by single worm tracks in the chronic phase. Blood-brain barrier leakages may subsequently occur due to a fibrinolytic system-dependent mechanism involving plasmin-dependent generation of the proinflammatory peptide bradykinin and activation of bradykinin B2 receptors, after different plasminogen-binding protein agglomeration waves. Interactions between diverse parasitic situations and non-imbalancing fibrinolysis system alterations are for the first time proposed that explain the complexity, heterogeneity and timely variations of neurological disorders. Additionally, inflammation and dilation of blood vessels may be due to contact system-dependent generation bradykinin. This baseline allows for search of indicators to detect neurological risk in fascioliasis patients and experimental work on antifibrinolytic treatments or B2 receptor antagonists for preventing blood-brain barrier leakage.

关键词： MCAO   Treadmill exercise   Caveolin-1/VEGF   Dendrite   Dendritic spine   Synaptic plasticity  

摘要： Dendritic and synaptic plasticity in the penumbra are important processes and are considered to be therapeutic targets of ischemic stroke. Treadmill exercise is known to be a beneficial treatment following stroke. However, its effects and potential mechanism in promoting dendritic and synaptic plasticity remain unknown. We have previously demonstrated that the caveolin-1/VEGF signaling pathway plays a positive role in angiogenesis and neurogenesis. Here, we further investigated the effects of treadmill exercise on promoting dendritic and synaptic plasticity in the penumbra and whether they involve the caveolin-1/VEGF signaling pathway. A middle cerebral artery occlusion (MCAO) animal model was established, and rats were randomly divided into eleven groups. At 2 days after MCAO, rats were subjected to treadmill exercise for 7 or 28 days. Daidzein (a specific inhibitor of caveolin-1, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated dendritic and synaptic plasticity. Neurobehavioral performance, tissue morphology and infarct volumes were detected by Modified Neurology Severity Score (mNSS), Hematoxylin-eosin (HE), and Nissl staining, while neural plasticity and its molecular mechanism were examined by Golgi-Cox staining, transmission electron microscopy, western blot analysis and immunofluorescence. We found that treadmill exercise promoted dendritic plasticity in the penumbra, consistent with the significant increase in caveolin-1 and VEGF expression;improved neurological recovery;and reduced infarct volume. In contrast to the positive effects of the treadmill, a caveolin-1 inhibitor abrogated the dendritic and synaptic plasticity. Furthermore, we observed that treadmill exercise-induced improved dendritic and synaptic plasticity were significantly inhibited by the caveolin-1 inhibitor, consistent with the lower expression of caveolin-1 and VEGF, as well as the worse neurobehavioral state. The findings indicate that treadmill

关键词： qualitative   brain injuries   nursing home   residential aged care   accommodation  

摘要： Background and aims: Previous research has highlighted that living in residential aged care (RAC) is associated with a range of negative outcomes for adults with acquired neurological disorders. This study sought to understand the lived experience of entering RAC for young people and their family members and characterise their needs during this process. Method: Data included 64 written and verbal submissions to the 2015 Senate Inquiry into the Adequacy of existing residential care arrangements available for young people with severe physical, mental or intellectual disabilities in Australia. In line with hermeneutic tradition, text was analysed using thematic analysis. Results: Entry to RAC was experienced as a complex process that coalesced around three key events: an unexpected health crisis, a directive that time's up and the individual is required to leave the healthcare setting, with a subsequent decision to move into RAC. This decision was made in the absence of time, knowledge of options or adequate support. Conclusions: Findings suggest that there are both immediate practice changes and longer term policy responses that can support the health and disability systems to uphold the rights of people with acquired disability to choose where and how they will live their lives.

关键词： alcohol   ataxia   Caine criteria   memory   thiamine   Wernicke's encephalopathy  

摘要： Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.

关键词： immunotherapy   neurotoxicity   polyneuropathy   myasthenia gravis   Bell's palsy   encephalopathy   nivolumab   pembrolizumab  

摘要： The advent of immune checkpoint inhibitors gave rise to a new era in oncology and general medicine. The increasing use of programmed death-1 (PD-1) inhibitors in non-small cell lung cancer and in other malignancies means clinicians have to face up to new challenges in managing immune-related adverse events (irAEs), which often resemble autoimmune diseases. Neurological irAEs represent an emerging toxicity related to immunotherapy, and it is mandatory to know how to monitor, recognize, and manage them, since they can rapidly lead to patient death if untreated. Guidelines for the diagnosis and treatment of these irAEs have been recently published but sharing some of the most unusual clinical cases is crucial, in our opinion, to improve awareness and to optimize the approach for these patients. A literature review on the diagnosis and treatment of immune-related neurotoxicity's has been conducted starting from the report of four cases of neurological irAEs regarding cases of polyneuropathy, myasthenia gravis, Bell's palsy, and encephalopathy, all of which occurred in oncological patients receiving PD-1 inhibitors (pembrolizumab and nivolumab) for the treatment of non-oncogene addicted advanced non-small cell lung cancer. The exclusion of other differential diagnoses and the correlation between the suspension of immunotherapy and improvement of symptoms suggest that immunotherapy could be the cause of the neurological disorders reported.

关键词： Hemolytic uremic syndrome   Neurological involvement   Eculizumab   Magnetic resonance imaging  

摘要： BackgroundThrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC).MethodsTMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with *** great clinical variability of brain injury in our cohort has led us to retrospectively build a neurological score useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI).ConclusionsA neurological score may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.

关键词： Out-of-hospital cardiac arrest   Emergency medical services   Cardiopulmonary resuscitation   Epiemiology  

摘要： Aim: The impact of prehospital physician care for out-of-hospital cardiac arrest (OHCA) on long-term neurological outcome is unclear. We aimed to determine the association between emergency medical services (EMS) physician-led cardiopulmonary resuscitation (CPR) versus paramedic-led CPR and neurologically intact survival after OHCA. Methods: We assessed 613,251 patients using All-Japan Utstein Registry data from 2011 to 2015 retrospectively. The main outcome measure was 1-month neurologically intact survival after OHCA, defined as Cerebral Performance Category 1 or 2 (CPC 1-2). Results: Before propensity score matching, the 1-month CPC 1-2 rate was significantly higher in EMS physician-led CPR than in paramedic-led CPR [5.7% (1114/19,551) vs. 2.5% (14,859/593,700), P < 0.001;adjusted odds ratio (aOR), 1.50;95% confidence interval (CI), 1.40-1.61]. After propensity score matching, EMS physician-led CPR showed more favourable neurological outcomes than paramedic-led CPR [6.0% (996/16,612) vs. 4.6% (766/16,612), P < 0.001;aOR, 1.44;95% CI, 1.29-1.60]. In most subgroup analyses after matching, physician-led CPR had higher 1-month CPC 1-2 rates than paramedic-led CPR did;however, 1-month CPC 1-2 rates were similar between the two CPR configurations for patients aged < 18 years (5.6% vs. 8.2%, P = 0.10;aOR, 0.82;95% CI, 0.46-1.47) and those who received bystander defibrillation (26.3% vs. 21.5%;P = 0.10;aOR, 1.07;95% CI, 0.74-1.53). Conclusion: Within the limitations of this retrospective observational research, EMS physician-led CPR for OHCA was associated with improved 1-month neurologically intact survival compared with paramedic-led CPR. However, neurologically intact survival was similar for patients aged < 18 years and those receiving bystander defibrillation.

摘要： High levels of antibodies against glutamic acid decarboxylase (GAD) are observed in patients with different neurological disorders, but cells producing these autoantibodies are largely unexplored. We detect circulating GAD-reactive B cells in peripheral blood that readily differentiate into antibody-producing cells. These cells are highly elevated in most patients with GAD-antibody-associated disorders (n = 15) compared to controls (n = 19). They mainly produce GAD65 antibodies of the IgG1 and IgG4 subclasses and are as abundant as B cells reactive for common recall antigens. Bone marrow cells represent an additional source of GAD antibodies. The identification of GAD-antibody-producing cells has implications for the selection of cell-specific biologics. ANN NEUROL 2019;85:448-454.

关键词： Spine surgery   Intraoperative neuromonitoring   Sensitivity   Specificity   Complications  

摘要： PurposeWe compared the value of different uni- and multimodal intraoperative neurophysiological monitoring (IONM) methods on the detection of neurological complications during spine *** data derived from sensory spinal and cortical evoked potentials combined with continuous electromyography monitoring, motor evoked potentials and spinal recording were evaluated in relation to subsequent post-operative neurological changes. Patients were categorised based on their true-positive or true-negative post-operative neurological *** 2728 consecutive patients we had 909 (33.3%) IONM alerts. We had 8 false negatives (0.3%) with post-operative radicular deficit that completely recovered within 3months, except for one. There was no false negative for spinal cord injury. 107 were true positives, and 23 were false positives. Multimodal IONM sensitivity and specificity were 93.0% and 99.1%, respectively. The frequency of neurological complications including minor deficits was 4.2% (n=115), of which 0.37% (n=10) were permanent. Analysis of the single IONM modalities varied between 13 and 81% to detect neurological complications compared with 93% when using all *** IONM is more effective and accurate in assessing spinal cord and nerve root function during spine surgeries to reduce both neurological complications and false-negative findings compared to unimodal monitoring. We recommend multimodal IONM in all complex spine surgeries. [GRAPHICS] .

摘要： Orthotopic liver transplantation (LT) remains the only way to definitively cure patients with the most severe liver diseases. Because the survival rate is now fairly high, important questions about neurological sequelae or quality of life after LT have emerged. Indeed, LT represents a peculiar situation because up to 30% of patients present with neurological symptoms after LT compared with only 4% after cardiac transplant and 0.5% after renal transplant. These postoperative neurological symptoms have long been interpreted as sequelae of hepatic encephalopathy (HE). However, postoperative decompensation of an unknown cerebral condition due to the pathophysiology of cirrhosis or undiagnosed neurodegenerative disorders or aging constitute other possibilities that are underrecognized. Some patients who undergo LT for acute liver failure and patients with cirrhosis without episodes of HE and without any previous cerebral alteration also display post-LT neurological symptoms. This latter situation speaks in favor of a direct adverse effect of either general anesthesia, the surgical procedure, or factors related to the postoperative intensive care unit (ICU) environment. The role of inflammation, which has been described in the ICU setting, could also be a crucial determinant. In this review, we will discuss the neurological complications associated with LT, the neurocognitive complications after LT, and how to assess the LT-related neurological or neurocognitive complications. Furthermore, we will review the various hypotheses surrounding post-LT neurocognitive impairment and will conclude with recommendations for future directions.