关键词： Cooling method   Targeted temperature management   Cardiac arrest   Outcome  

摘要： Objective: The purpose of this study was to determine whether the cooling method used for target temperature management (TTM) was associated with neurological recovery after out-of-hospital cardiac arrest (OHCA). Methods: From January 2008 to December 2016, adult OHCA patients who survived to hospitalization without any traumatic etiology and who received TTM were included. Patients who did not have information about neurological status at hospital discharge or who did not have information on target temperature management were excluded. Cooling methods were classified into four groups: (1) external device cooling (EDC) using a pad with cooling device, (2) external conventional cooling (ECC) such as ice water, fans, and simple blankets, (3) Intravascular cooling (IVC) using an intravascular cooling catheter, and (4) intracavitary cooling (ICC) using ice water for washing cavitary organ. The outcomes were good cerebral performance scale (CPC) score 1 or 2 and survival to discharge. In multivariate logistic regression analysis, the adjusted odds ratios (AORs) and the 95% confidence intervals (CIs) were calculated (reference = ECC). Finally, we used a GLIMMIX procedure with group-level variables (hospitals) to create a multilevel model for adjusting the clustering factor of patients being treated in the same hospital. Results: The final analysis included a total of 4246 eligible patients (ECC 1386, EDC 2107, IVC 376, ICC 377). Good neurologic recovery was 20.7% for all (ECC 17.4, EDC 23.1%, IVC 26.9%, and ICC 13.3%, p < .001). The survival rate was 46.4% for all (ECC 45.4%, EDC 48.5%, IVC 50.5%, ICC 34.2%, p < .001). There were no significant differences (AOR and 95% CI) in the multi-level analysis for good neurological recovery between cooling methods compared with ECC;EDC 1.20 (0.95-1.52), IVC 1.43 (0.90-2.27), and ICC 0.71 (0.46-1.10). The ICC group had a lower survival to discharge rate compared with ECC;EDC 0.97 (0.83-1.15), IVC 0.96 (0.78-1.19), and ICC 0.63 (0.43

关键词： DNM1L   DRP-1   Mitochondrial fission   Oxidative function  

摘要： Mitochondria play vital roles in brain development and neuronal activity, and mitochondrial dynamics (fission and fusion) maintain organelle function through the removal of damaged components. Dynamin-like protein-1 (DRP-1), encoded by DNM1L, is an evolutionarily conserved GTPase that mediates mitochondrial fission by surrounding the scission site in concentric ring-like structures via self-oligomerization, followed by GTPase-dependant constriction. Here, we describe the clinical characteristics and cellular phenotype of a patient with severe neurological dysfunction, possessing a homozygous DNM1L variant c.305C > T (p.T115M) in the GTPase domain. For comparative analysis, we also describe a previously identified heterozygous variant demonstrating a rapidly fatal neurocognitive phenotype (c.261dup/c.385:386del, p.W88M*9/E129K*6). Using patient-generated fibroblasts, we demonstrated both DNM1L variants undergo adverse alterations to mitochondrial structure and function, including impaired mitochondrial fission, reduced membrane potential, and lower oxidative capacity including an increased cellular level of reactive oxygen species (ROS) and dsDNA breaks. Mutation of DNM1L was also associated with impaired responses to oxidative stress, as treatment with hydrogen peroxide dramatically increased cellular ROS, with minimal exacerbation of already impaired mitochondrial function. Taken together, our observations indicate that homozygous p.T115M variant of DNM1L produces a neurological and neurodevelopmental phenotype, consistent with impaired mitochondrial architecture and function, through a diminished ability to oligomerize, which was most prevalent under oxidative stress.

关键词： Human papillomavirus   vaccine safety   epidemiology   autoimmune diseases   neurological diseases   venous   thromboembolism  

摘要： Background: In recent years, human papillomavirus (HPV) vaccination of boys has been added to childhood vaccination programmes in several countries but, so far, no systematic population-based assessment with long-term follow-up has been undertaken of the relative incidence of adverse outcomes following HPV vaccination in this group. We investigated if quadrivalent HPV (qHPV) vaccination of 10-17-year-old boys is associated with any unusual risk of autoimmune diseases, neurological diseases or venous thromboembolism. Methods: We conducted a national cohort study of 568 410 boys born in Denmark 1988-2006 and followed for 4 million person-years during 2006-16, using nationwide registers to obtain individual-level information about received doses of the qHPV vaccine and hospital records for 39 autoimmune diseases, 12 neurological diseases and venous thromboembolism. For each outcome, we estimated incidence rate ratios (RRs) with 95% confidence intervals (CIs) according to qHPV vaccination status. Results: Altogether 7384 boys received at least one dose of the qHPV vaccine at age 10-17 years. Overall, RRs were close to unity for the combined groups of autoimmune diseases (RR = 0.96;95% CI: 0.71-1.28, n = 46 cases in qHPV- vaccinated boys) and neurological diseases (RR = 0.67;0.41-1.10, n = 16), as well as for venous thromboembolism (RR = 0.88;0.33-2.35, n - 4). After taking multiple testing into account, none of the 52 individual outcomes studied appeared to occur in excess among qHPV- vaccinated boys. Conclusions: Although additional large-scale epidemiological studies are warranted, our findings provide population- based reassurance that qHPV vaccination of 10-17-year-old boys is unlikely to be associated with an elevated risk of autoimmune diseases, neurological diseases or venous thromboembolism.

关键词： PEA   Non-shockable   Pulseless electrical activity   Resuscitation   OOHCA   Survival   Prognosis   Outcome  

摘要： Background: Outcome is generally poor in out of hospital cardiac arrests (OHCA) with initial non-shockable rhythms. Termination of resuscitation rules facilitate early prognostication at the scene to cease resuscitation attempts in futile situations and to proceed advanced life support in promising conditions. As pulseless electrical activity (PEA) is present as first rhythm in every 4th OHCA we were interested if the initial electrical frequency in PEA predicts survival. Methods: All patients > 18 years of age with non-traumatic OHCA and PEA as first rhythm between August 2013 and August 2015 from the Vienna Cardiac Arrest Registry were included in this retrospective observational study. Defibrillator and epidemiological data from the emergency medical system as survival data were processed considering the initial electrical activity in PEA and 30 days survival. Results: Out of 2149 OHCA patients, a total of 504 PEA patients were eligible for analyses. These patients were stratified into 4 groups according the initial electrical frequency in PEA: 10-24/min, 25-39/min, 40-59/min, > 60/min. Compared to a frequency > 60/min all other subgroups were associated with higher mortality especially those with an initial electrical frequency 10-24 (adjusted OR 0.56 (0.39-0.79) p =. 001 for each category chance). QRS duration in PEA did not influence outcome. Patients in the > 60/min group showed a 30-days-survival rate of 22% and a good neurological outcome in 15% of all patients - comparable to shockable cardiac arrest rhythms. Conclusion: Regardless of other resuscitation factors, higher initial electrical frequency in PEA is associated with increased odds of survival and good neurological outcome.

关键词： acute lymphoid leukaemia   aspergillosis   drug-drug interaction   neurotoxicity   paediatric pharmacokinetics  

摘要： What is known and objectiveVoriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. Case descriptionWe report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains. It shows the high variability of the trough serum concentration of voriconazole leading to antifungal treatment failure and suggests that its own central neurotoxicity could also be potentiated by vincristine. What is new and conclusionGiven the risk of either insufficient antifungal efficacy or excessive neurological disorders, this case warns on a probable unfavourable risk-benefit profile of voriconazole during vincristine-based chemotherapy in adolescents.

关键词： Computed tomography angiography   neuroimaging   acute headache   thunderclap headache   meta analysis  

摘要： Background: Patients with acute severe headache, normal neurological examination, and a normal noncontrast head computed tomography (NCCT) may still have subarachnoid hemorrhage, cerebral venous thrombosis (CVT), cervical arterial dissection, or reversible cerebral vasoconstriction syndrome (RCVS). Computed tomography angiography (CTA) is used increasingly in the emergency department for evaluating this, but its added value remains controversial. Methods: We retrospectively collected data on the diagnostic yield of CTA in patients with acute severe headache, normal neurological examination, and normal NCCT who received additional CTA in the acute phase in 2 secondary referral centers for vascular neurology. We combined data of our patients with those from the literature and performed a meta-analysis. Results: We included 88 patients from our hospital files and 641 patients after literature search. Of 729 patients 54 had a vascular abnormality on CTA (7.4%;95% confidence interval [CI] 5.5%-9.3%). Abnormalities consisted of aneurysms (n = 42;5.4%;95% CI 3.8%-7.0%), CVT (n = 3,.5%), RCVS (n = 4,.5%), Moyamoya syndrome (n = 2,.3%), arterial dissection (n = 2,.3%), and ischemia (n = 1,.1%). Because most of the aneurysms were probably incidental findings, only 12 (1.6%) patients had a clear relation between the headache and CTA findings. The number needed to scan to find an abnormality was 14 overall, and 61 for an abnormality other than an aneurysm. Conclusion: Diagnostic yield of CTA in patients with acute headache, normal neurological examination, and normal NCCT is low, but because of the possible therapeutic consequences, its use might be justified in the emergency setting. Prospective studies confirming these results including cost-effectiveness analyses are needed.

关键词： Conversion disorder   Psychogenic nonepileptic seizures   Functional movement disorders   Resilience   Personality  

摘要： Objective: Reduced resilience, a construct associated with maladaptive stress coping and a predisposing vulnerability for Functional Neurological Disorders (FND), has been under-studied compared to other neuropsychiatric factors in FND. This prospective case-control study investigated self-reported resilience in patients with FND compared to controls and examined relationships between resilience and affective symptoms, personality traits, alexithymia, health status and adverse life event burden. Methods: 50 individuals with motor FND and 47 healthy controls participated. A univariate test followed by a logistic regression analysis investigated group-level differences in Connor-Davidson Resilience Scale (CD-RISC) scores. For within-group analyses performed separately in patients with FND and controls, univariate screening tests followed by multivariate linear regression analyses examined factors associated with self-reported resilience. Results: Adjusting for age, gender, education status, ethnicity and lifetime adverse event burden, patients with FND reported reduced resilience compared to controls. Within-group analyses in patients with FND showed that individual-differences in mental health, extraversion, conscientiousness, and openness positively correlated with CD-RISC scores;post-traumatic stress disorder symptom severity, depression, anxiety, alexithymia and neuroticism scores negatively correlated with CD-RISC scores. Extraversion independently predicted resilience scores in patients with FND. In control subjects, univariate associations were appreciated between CD-RISC scores and gender, personality traits, anxiety, alexithymia and physical health;conscientiousness independently predicted resilience in controls. Conclusion: Patients with FND reported reduced resilience, and CD-RISC scores covaried with other important predisposing vulnerabilities for the development of FND. Future research should investigate if the CD-RISC is predictive of clinical outcomes

关键词： global neurology   global health neurology  

摘要： Neurology has not typically been associated with international relief work;however, with the growth of chronic cardiovascular disease and stroke associated with unhealthy eating and sedentary ways, the appearance of new neurologic diseases, such as the Zika and West Nile viruses, and the high numbers of seizure disorders resulting from neuroinfectious diseases, more opportunities are arising for international and globally oriented neurologists. Multiple opportunities exist for developing a global clinician-educator career pathway, including private institutions, nongovernmental organizations, government-funded opportunities such as Medical Education Partnership Initiative, Fogarty and Fulbright Scholarships, and the American Academy of Neurology's Global Health Section. Furthermore, increasing research capacity in developing countries and increased funding opportunities for global health research have led to new opportunities for neurologists to establish global health research careers. These opportunities could not have come at a better time, as many faculty members have noted a particularly strong interest in global neurology from medical students and residents. Career categories and opportunities for neurologists desiring to work globally are discussed along with the emerging global neurologist academic pathway.

关键词： DIFFUSION kinetics   NEUROLOGIC examination   CORONARY heart disease diagnosis   CARDIAC arrest etiology   TREATMENT of cardiac arrest  

摘要： Background Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome. Methods This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ***,number NCT00577954. Findings Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0.95, 95% CI 0.91-0.98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31,

关键词： Dexmedetomidine   Aneurysmal subarachnoid hemorrhage   Neurological outcome  

摘要： Purpose: Recent studies in animal subarachnoid hemorrhage (SAH) models have reported that dexmedetomidine (DEX) use demonstrates significantly better neurological outcomes. This study aimed to evaluate whether DEX use is associated with favorable neurological outcomes (FO) in SAH patients. Materials and methods: We retrospectively reviewed all SAH patients between 2009 and 2017. We calculated the total dosage of DEX administered for the first 24 h after admission. All patients were classified into no use, low dosage, and standard dosage group. Multivariate analysis was performed to clarify the association between DEX use and FO (modified Ranking Scale score of 0-2 at hospital discharge). Results: There were 161 patients with 55.3% of FO. On univariate analysis, there were significant differences with regard to age, Hunt and Kosnik (H&K) grade, and DEX use. Multivariate analysis showed that age, H&K grade, and low dosage DEX (rather than no use) (odds ratio (OR) 3.17;95% confidence interval (CI), 1.24-8.53;p = 0.02) were significantly associated with FO. However, standard dosage DEX was not a significant factor (OR, 0.75;95% CI, 0.25-2.16;p = 0.59). Conclusions: Low dosage DEX during the first 24 h after admission was associated with FO in SAH patients. (C) 2017 Elsevier Inc. All rights reserved.