关键词： inborn errors of metabolism   neurological sequelae   refugee medicine   newborn screening   phenylketonuria   biotinidase deficiency  

摘要： In the 2015 mass migration from Syria and neighboring countries, Germany received an unprecedented number of 4,76,649 asylum applications. As many of the refugees arrived in Southern Germany via the Austrian border, the city of Munich was faced with the majority of Germany's inflow of war refugees and their complex health issues. Among the refugees were a high number of children. Their main health issues were infectious diseases and surgical procedures due to trauma, but we also encountered complex chronic diseases. This report describes clinical history, signs and symptoms, diagnostics, and treatment of six pediatric patients with untreated inborn errors of metabolism (IEM): phenylketonuria, biotinidase deficiency, HMG-CoA lyase deficiency, mucopolysaccharidosis type It, and mucopolysaccharidosis type VI. Since early diagnosis and treatment is essential in IEM, both delayed diagnosis and inadequate therapy in refugee children may lead to significant brain injury, organ damage, and even death. Severe neurological sequelae in both phenylketonuria and HMG-CoA lyase deficiency could have been prevented by newborn screening. Screening programs are necessary to improve the prognoses for refugee children. European Union governments and involved health care systems should pursue early diagnosis and treatment in pediatric refugees regarding IEM to prevent neurological long-term sequelae.

关键词： quinine   quinidine   cinchona   malaria   atrial fibrillation   Brugada syndrome   prolonged QT syndrome   restless leg syndrome   Alzheimer's disease   epilepsy  

摘要： This article describes the discovery and use of the South American cinchona bark and its main therapeutic (and toxic) alkaloids, quinine and quinidine. Since the introduction of cinchona to Europe in the 17th century, it played a role in treating emperors and peasants and was central to colonialism and wars. Over those 400 years, the medical use of cinchona alkaloids has evolved from bark extracts to chemical synthesis and controlled clinical trials. At the present time, the use of quinine and quinidine has declined, to a large extent due to their toxicity. However, quinine is still being prescribed in resource-limited settings, in severe malaria, and in pregnant women, and quinidine made a limited comeback in the treatment of several cardiac and neurological syndromes. In addition, the article presents more recent studies which improved our understanding of cinchona alkaloids' pharmacology. The knowledge gained through these studies will hopefully lead to a wider use of these drugs in precision medicine and to design of new generation, safer quinine and quinidine derivatives.

关键词： Cardiac arrest   Prognosis   Outcome  

摘要： Aim: Although various quantitative methods have been developed for predicting neurological prognosis in patients with out-of-hospital cardiac arrest (OHCA), they are too complex for use in clinical practice. We aimed to develop a simple decision rule for predicting neurological outcomes following the return of spontaneous circulation (ROSC) in patients with OHCA using fast-and-frugal tree (FFT) analysis. Methods: We performed a retrospective analysis of prospectively collected data archived in a multi-centre registry. Good neurological outcomes were defined as cerebral performance category (CPC) values of 1 or 2 at 28 day. Variables used for FFT analysis included age, sex, witnessed cardiac arrest, bystander cardiopulmonary resuscitation, initial shockable rhythm, prehospital defibrillation, prehospital ROSC, no flow time, low flow time, cause of arrest (cardiac or non-cardiac), pupillary light reflex, and Glasgow Coma Scale score after ROSC. Results: Among the 456 patients enrolled, 86 (18.9%) experienced good neurological outcomes. Prehospital ROSC (true = good), prompt or sluggish light reflex response after ROSC (true = good), and presumed cardiac cause (true = good, false = poor) were selected as nodes for the decision tree. Sensitivity, specificity, positive predictive value, and negative predictive value of the decision tree for predicting good neurological outcomes were 100% (42/42), 64.0% (119/186), 38.5% (42/109), and 100% (119/119) in the training set and 95.5% (42/44), 57.6% (106/184), 35.0% (42/120), and 98.1% (106/108) in the test set, respectively. Conclusion: A simple decision rule developed via FFT analysis can aid clinicians in predicting neurological outcomes following ROSC in patients with OHCA.

关键词： Resident   Continued education   Feedback   Personnel congestion   Economic pressure  

摘要： Background. Currently, no data are available, which reflect the situation of medical doctors specializing in neurology in German hospitals. In order to secure the high standard of neurological patient care it is essential to evaluate the working conditions and the specialty training in neurology. Objective. This nationwide survey was conducted throughout Germany with the aim to address problems and to give suggestions for improvements in neurological training curricula. Material and methods. The survey was online from February to May 2017 and 953 neurologists undergoing further training participated. Results. More than half of the young neurologists were satisfied with their medical training. One of the main problems that complicates clinical training is the workload. In addition, organizational obstacles within the clinic, such as poor structure of education or a lack of mentors, lead to dissatisfaction among participants. The size or type of the department, as well as the prevailing service system, exert only a minor influence on the quality of specialist training, although there were differences especially in the self-assessment of the participants in connection with the type of department (university hospital versus public or private hospital). Conclusion. Specialist training in neurology can be improved by simple arrangements, e.g., the introduction of a binding rotation scheme, internal mentoring and structured feedback. In addition, it will be necessary to relieve medical staff of administrative duties in order to create time for training and the learning of competencies.

关键词： Acquired neurological disorders   Traumatic brain injury (TBI)   Stroke   Spinal cord injury (SCI)   Exosomes   Extracellular vesicles  

摘要： Exosomes are endogenous nanovesicles that play critical roles in intercellular signaling by conveying functional genetic information and proteins between cells. Exosomes readily cross the blood-brain barrier and have promise as therapeutic delivery vehicles that have the potential to specifically deliver molecules to the central nervous system (CNS). This unique feature also makes exosomes attractive as biomarkers in diagnostics, prognostics, and therapeutics in the context of multiple significant public health conditions, including acquired neurological disorders. The purpose of this review is to summarize the state of the science surrounding the relevance of extracellular vesicles (EVs), particularly exosomes, to acquire neurological disorders, specifically traumatic brain injury (TBI), spinal cord injury (SCI), and ischemic stroke. In total, ten research articles were identified that examined exosomes in the context of TBI, SCI, or stroke;these manuscripts were reviewed and synthesized to further understand the current role of exosomes in the context of acquired neurological disorders. Of the ten published studies, four focused exclusively on TBI, one on both TBI and SCI, and five on ischemic stroke;notably, eight of the ten studies were limited to pre-clinical samples. The present review is the first to discuss the current body of knowledge surrounding the role of exosomes in the pathophysiology, diagnosis, and prognosis, as well as promising therapeutic strategies in TBI, SCI, and stroke research.

关键词： Congenital toxoplasmosis   Toxoplasma gondii   Hydrocephalus   Retinochoroiditis   Diagnosis   Treatment  

摘要： Toxoplasma gondii is an obligate intracellular parasite which is known to infect one-third of the total world population chronically though it is asymptomatic in immunocompetent patients. However, in an immunocompromised patient or an infected fetus, it may cause devastating effects. The parasite may cross the placenta of an infected pregnant woman and probably infect the fetus congenitally. The severity of the infection depends on the gestational age at which the infection has occurred i.e., if it has occurred in the early phase, the rate of transmission is low but the severity is high if the fetus is infected and if it has occurred in the later phase then transmission rate is higher while the severity would be low. Congenital toxoplasmosis may result in nonspecific consequences like abortion, intra-uterine growth restriction, jaundice, hepatosplenomegaly or even intra-uterine death. It may also result in neurological or ocular manifestations like intracranial calcifications, hydrocephalus or retinochoroiditis. The diagnosis may be done by serological screening of anti-Toxoplasma antibodies (IgM and IgG) while PCR of the amniotic fluid or the placenta is the confirmatory test. Acute or chronic infections may be differentiated by IgG avidity tests. The treatment regimens include spiramycin to prevent congenital transmission from an infected mother, pyrimethamine, sulfadoxine and folinic acid to treat the infected fetus, CSF shunting for the treatment of hydrocephalus and a combination of pyrimethamine, azithromycin, and corticosteroids for treating ocular toxoplasmosis.

关键词： Cardiac arrest   Hypoxic ischemic brain injury   Targeted-temperature management   Long-term outcomes   Cognitive scales  

摘要： Background: This study aimed to assess long-term cognitive and functional outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted-temperature management, investigate the existence of prognostic factors that could be assessed during initial admission and evaluate the usefulness of classic neurological scales in this clinical scenario. Methods: Patients admitted due to OHCA from August 2007 to November 2015 and surviving at least one year were included. Each patient completed a structured interview focused on the collection of clinical, social and demographic data. All available information in clinical records was reviewed and a battery of neurocognitive and psychometric tests was performed. Results: Seventy-nine patients were finally included in the analysis. Forty-three patients (54.4%) scored below the usual cut-off points for the diagnosis of mild cognitive impairment, even though most of these deficits went unnoticed when patients were assessed using CPC and modified Rankin scale. Nineteen (24%) developed certain degree of impairment in their attention capacity and executive functions. A significant proportion developed new memory-related disorders (43%), depressive symptoms (17.7%), aggressive/uninhibited behavior (12.7%) and emotional lability (8.9%). A greater number of weekly hours of intellectual activity and a qualified job were independent protective factors for the development of cognitive impairment. However, being older at the time of the cardiac arrest was identified as a poor prognostic factor. Conclusions: There is a high prevalence of long-term cognitive deficits and functional limitations in OHCA survivors. Most commonly used clinical scales in clinical practice are crude and lack sensitivity to detect most of these deficits.

关键词： Thoracolumbar fracture   Incomplete burst fracture   Randomized trial   Sample-size calculation   Posterior-anterior stabilization  

摘要： Purpose If surgery for thoracolumbar incomplete cranial burst fractures (Magerl A3.1.1) is necessary, the ideal stabilization strategy still remains undetermined. To justify posterior-anterior stabilization, which generates higher costs and potentially higher morbidity vs. posterior-only stabilization, clinical trials with sufficient power and adequate methodology are required. This prospective randomized single-centre pilot trial was designed to enable sufficient sample-size calculation for a randomized multicentre clinical trial (RASPUTHINE). Methods Patients with a traumatic thoracolumbar (Th11-L2) incomplete burst fracture (Magerl A3.1.1) were randomly assigned either to the interventional group (posterior-anterior) or to the control group (posterior-only). Primary endpoint of the study was the clinical outcome measured using the Oswestry Disability Index (ODI) at 24 months. Radiological outcome was assessed as secondary endpoint by evaluation of mono- and bisegmental kyphotic angulation and monosegmental fusion. Results 21 patients were randomly assigned to interventional group (n = 9) or control group (n = 12). One posterior-only treated patient showed a severe initial loss of correction resulting in a crossover to additional anterior bisegmental fusion. The ODI measures at the primary study endpoint showed less but insignificant (p = 0.67) disability for the interventional group over the control group (13.3 vs. 19.3%). Comparison of preoperative bisegmental kyphosis in supine position with the bisegmental kyphosis at 24-month FU in upright position showed a worsened kyphosis for the control group (10.7 degrees -> 15.6 degrees), whereas an improved kyphosis (11 degrees -> 8.3 degrees) was detectable for the interventional group. Conclusion The results of this pilot RCT showed less disability for the posterior-anterior group linked with a significant better restoration of the sagittal profile in comparison with the posterior-only group. To detect a clinically s

关键词： Out of hospital cardiac arrest   Ventilation   Hemodynamic monitoring   Vital signs   Prehospital emergency care  

摘要： Introduction: The targets for vital parameters following return of spontaneous circulation (ROSC) from an out-of-hospital cardiac arrest (OHCA) are based on studies carried out predominantly in intensive care units. Therefore, we studied the pre-hospital phase. Method: We included all adult OHCA from the French OHCA Registry. Vital parameters [peripheral oxygen saturation level (SpO(2)), end-tidal carbon dioxide (ETCO2) and systolic blood pressure (SBP)] documented during the pre-hospital phase by mobile medical team, were evaluated with regard to the neurological outcome on day 30 (classified as good for Cerebral Performance Category (CPC) 1 - 2, and poor for CPC 3 - 5 or death). Results: When compared with a reference range of 94-98%, SpO(2) values less than 94% were associated with a worse outcome on univariate analysis [relative risk (RR) = 1.108(1.069-1.147)]. An SpO(2) of 99 - 100% did not appear to be harmful [RR = 0.9851(0.956-1.015)]. ETCO2 values that deviated from the reference of 30-40 mmHg were associated with a worse outcome on univariate analysis [< 20, RR = 1.191(1.143-1.229);20-29, RR = 1.092(1.061-1.123);41-50, RR = 1.075(1.039-1.110);> 50, RR = 1.136(1.085-1.179)]. When compared with a reference range of 100-130, higher or lower values of SBP were associated with a worse outcome on univariate analysis [< 80, RR = 1.203(1.158-1.243);80-99, RR = 1.069(1.033-1.105);131-160, RR = 1.076(1.043-1.110);> 160, RR = 1.168(1.126 - 1.208)]. The multivariate analysis yielded similar results. Conclusion: In comatose patients who have achieved ROSC after OHCA, vital parameters in the pre-hospital phase appear to have a real impact on the 30-day neurological outcome. We found that an SpO(2) >= 94%, an ETCO2 of 30 - 40 mmHg, and an SBP of 100 - 130 mmHg were associated with a better prognosis.

关键词： Out-of-hospital cardiac arrest   Epinephrine   Cardiopulmonary resuscitation   Cardiopulmonary resuscitation duration   Neurological outcome  

摘要： The effects of prehospital epinephrine administration on post-arrest neurological outcome in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm remain unclear. To examine the time-dependent effectiveness of prehospital epinephrine administration, we analyzed 118,396 bystander-witnessed OHCA patients with non-shockable rhythm from the prospectively recorded all-Japan OHCA registry between 2011 and 2014. Patients who achieved prehospital return of spontaneous circulation without prehospital epinephrine administration were excluded. Patients with prehospital epinephrine administration were stratified according to the time from the initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers to the first epinephrine administration (10, 11-19, and 20min). Patients without prehospital epinephrine administration were stratified according to the time from CPR initiation by EMS providers to hospital arrival (10, 11-19, and 20min). The primary outcome was 1-month neurologically intact survival (cerebral performance category 1 or 2;CPC 1-2). Multivariate logistic regression analysis demonstrated that there was no significant difference in the chance of 1-month CPC 1-2 between patients who arrived at hospital in 10min without prehospital epinephrine administration and patients with time to epinephrine administration 19min. However, compared to patients who arrived at hospital in 10min without prehospital epinephrine administration, patients with time to epinephrine administration 20min and patients who arrived at hospital in 11-19, and 20min without prehospital epinephrine administration were significantly associated with decreased chance of 1-month CPC 1-2 (p<0.05, <0.05, and <0.001, respectively). In conclusion, when prehospital CPR duration from CPR initiation by EMS providers to hospital arrival estimated to be11min, prehospital epinephrine administered19min from CPR initiation by EMS providers could improve neurologic