关键词： Virtual interviews   Residency application   Graduate medical education   Match   Survey  

摘要： Background: The COVID-19 pandemic presented many challenges for graduate medical education, including the need to quickly implement virtual residency interviews. We investigated how different programs approached these challenges to determine best practices. Methods: Surveys to solicit perspectives of program directors, program coordinators, and chief residents regarding virtual interviews were designed through an iterative process by two child neurology resi-dency program directors. Surveys were distributed by email in May 2021. Results were summarized using descriptive statistics. Results: Responses were received from 35 program directors and 34 program coordinators from 76 programs contacted. Compared with the 2019-2020 recruitment season, in 2020-2021,14 of 35 programs received >10% more applications and most programs interviewed >12 applicants per position. Interview days were typically five to six hours long and were often coordinated with pediatrics interviews. Most programs (13/15) utilized virtual social events with residents, but these often did not allow residents to provide quality feedback about applicants. Program directors could adequately assess most applicant qualities but felt that virtual interviews limited their ability to assess applicants' interpersonal communication skills and to showcase special features of their programs. Most respondents felt that a combination of virtual and in-person interviewing should be utilized in the future. Conclusions: Residency program directors perceived some negative impacts of virtual interviewing on their recruitment efforts but in general felt that virtual interviews adequately replaced in-person in-terviews for assessing applicants. Most programs felt that virtual interviewing should be utilized in the future. (c) 2021 Elsevier Inc. All rights reserved.

关键词： clinical exome sequencing   cost analysis   diagnostics   neurological disease  

摘要： Objectives Clinical diagnostics in adults with hereditary neurological diseases is complicated by clinical and genetic heterogeneity, as well as lifestyle effects. Here, we evaluate the effectiveness of exome sequencing and clinical costs in our difficult-to-diagnose adult patient cohort. Additionally, we expand the phenotypic and genetic spectrum of hereditary neurological disorders in Finland. Methods We performed clinical exome sequencing (CES) to 100 adult patients from Finland with neurological symptoms of suspected genetic cause. The patients were classified as myopathy (n = 57), peripheral neuropathy (n = 16), ataxia (n = 15), spastic paraplegia (n = 4), Parkinsonism (n = 3), and mixed (n = 5). In addition, we gathered the costs of prior diagnostic work-up to retrospectively assess the cost-effectiveness of CES as a first-line diagnostic tool. Results The overall diagnostic yield of CES was 27%. Pathogenic variants were found for 14 patients (in genes ANO5, CHCHD10, CLCN1, DES, DOK7, FKBP14, POLG, PYROXD1, SCN4A, TUBB3, and TTN) and likely pathogenic previously undescribed variants for 13 patients (in genes ABCD1, AFG3L2, ATL1, CACNA1A, COL6A1, DYSF, IRF2BPL, KCNA1, MT-ATP6, SAMD9L, SGCB, and TPM2). Age of onset below 40 years increased the probability of finding a genetic cause. Our cost evaluation of prior diagnostic work-up suggested that early CES would be cost-effective in this patient group, in which diagnostic costs increase linearly with prolonged investigations. Conclusions Based on our results, CES is a cost-effective, powerful first-line diagnostic tool in establishing the molecular diagnosis in adult neurological patients with variable symptoms. Importantly, CES can markedly shorten the diagnostic odysseys of about one third of patients.

关键词： Mitochondria   Iron-sulfur cluster   Iron-sulfur cluster biogenesis disorder   Neuroimaging   Friedreich ataxia   Neurology  

摘要： Iron-sulfur clusters (ISCs) are highly conserved moieties embedded into numerous crucial proteins in almost all bacteria, plants and mammals. As such, ISC biosynthesis is critical to cellular function. The pathway was first characterized in bacteria by the late 1990s, and over the subsequent 20 years there has been increasing understanding of its components in humans. Defects in the ISC pathway are now associated with many different human disease states, such as Friedreich ataxia and ISCU myopathy. Whilst the disorders have variable clinical features, most involve neurological phenotypes. There are common biochemical signatures in most of these conditions, as a lack of ISCs causes deficiencies of target proteins including Complex I, II and III, aconitase and lipoic acid. This review focuses on the disorders of ISC biogenesis that have been described in the literature to-date. Key clinical, biochemical and neuroradiological features will be discussed, providing a reference point for clinicians diagnosing and managing these patients. Therapies are mostly supportive at this stage. However, the improved understanding of the pathophysiology of these conditions could pave the way for disease-modifying therapies in the near future.

关键词： Congenital heart disease (CHD)   Neurodevelopmental   Magnetic resonance imaging (MRI)   Stroke   Outcome  

摘要： The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10 weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12 months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment >= to 12 months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.

关键词： Outcomes research   Physical examination   Spinal cord diseases   Biomedicine   general   Neurosciences   Anatomy   Human Physiology   Neurochemistry   Neuropsychology  

摘要： Study design Prospective pre-post study. Objectives International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) represents the most frequently used assessment to determine the level and severity of a spinal cord injury (SCI). The guidelines for ISNCSCI are complex and challenging. Knowledge of its correct execution needs to be imparted precisely. The aim of this study was to investigate whether hands-on instructional courses can increase the knowledge of the ISNCSCI examination guidelines. Setting European Multicenter Study about SCI. Methods Before and after the instructional courses, participants were asked to complete questionnaires. The set of questions covered the most important aspects of the examination guidelines. Attendees were asked to self-rate their occupation and experience in ISNCSCI. Results The comparison of pretest and posttest results of 164 attendees from 2014 to 2018 revealed an improvement of knowledge reflected by an increase of correct answers from 66 +/- 17% before to 89 +/- 11% after the course (p < 0.01). The improvement was not associated with occupation (p > 0.1). However, the correctness of pretest results differed concerning both the period of experience with ISNCSCI (p < 0.05) and the course language (p < 0.01), while the frequency of execution resulted in differences in the posttest (p = 0.01). Conclusions Instructional courses substantially improve knowledge of the ISNCSCI examination guidelines. Differences in knowledge present before the course leveled off after the course. Comprehensive theoretical training is strongly recommended to ensure reliability and validity of ISNCSCI examinations in clinical routine and research. Albeit being practiced in the instructional courses, the benefit of hands-on training still needs to be systematically evaluated in future studies.

关键词： Human Genetics   Molecular Medicine   Gene Function   Metabolic Diseases  

摘要： The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters, adenosine 5 '-triphosphate (ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells. SLCs play an important role in maintaining normal brain function. Hence, mutations in the genes that encode SLC transporters can cause a variety of neurological disorders. We identified the following SLC gene variants in 25 patients in our cohort: SLC1A2, SLC2A1, SLC5A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC12A6, SLC13A5, SLC16A1, SLC17A5, SLC19A3, SLC25A12, SLC25A15, SLC27A4, SLC45A1, SLC46A1, and SLC52A3. Eight patients harbored pathogenic or likely pathogenic mutations (SLC5A1, SLC9A6, SLC12A6, SLC16A1, SLC19A3, and SLC52A3), and 12 patients were found to have variants of unknown clinical significance (VOUS);these variants occurred in 11 genes (SLC1A2, SLC2A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC13A5, SLC25A12, SLC27A4, and SLC45A1). Five patients were excluded as they were carriers. In the remaining 20 patients with SLC gene variants, we identified 16 possible distinct neurological disorders. Based on the clinical presentation, we categorized them into genes causing intellectual delay (ID) or autism spectrum disorder (ASD), those causing epilepsy, those causing vitamin-related disorders, and those causing other neurological diseases. Several variants were detected that indicated possible personalized therapies: SLC2A1 led to dystonia or epilepsy, which can be treated with a ketogenic diet;SLC6A3 led to infantile parkinsonism-dystonia 1, which can be treated with levodopa;SLC6A5 led to hyperekplexia 3, for which unnecessary treatment with antiepileptic drugs should be avoided;SLC6A8 led to crea

关键词： Alzheimer's disease   Angiotensin-converting enzyme 2 (ACE2) receptor   Coronavirus   COVID-19   CoV-19   Hartnup's disease   microRNA   miRNA-5197   SARS-CoV-2   single stranded RNA (ssRNA)  

摘要： The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. SARS-CoV-2, that causes coronavirus disease 2019 (COVID-19;CoV-19) has the unusual capacity to attack many different types of human host cells simultaneously via novel clathrin- and caveolae-independent endocytic pathways, becoming injurious to diverse cells, tissues and organ systems and exploiting any immune weakness in the host. The elicitation of this multipronged attack explains in part the severity and extensive variety of signs and symptoms observed in CoV-19 patients. To further our understanding of the mechanism and pathways of SARS-CoV-2 infection and susceptibility of specific cell- and tissue-types and organ systems to SARS-CoV-2 attack in this communication we analyzed ACE2 expression in 85 human tissues including 21 different brain regions, 7 fetal tissues and 8 controls. Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem. The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress.

关键词： adverse reaction   COVID-19   neuropathy   SARS-CoV-2   side effect   vaccination  

摘要： SARS-CoV-2 and adverse reactions to SARS-CoV-2 vaccinations show a tropism for neuronal structures and tissues. This narrative review was conducted to collect and discuss published data about neurological side effects of SARS-CoV-2 vaccines in order to discover type, frequency, treatment, and outcome of these side effects. The most frequent neurological side effects of SARS-CoV-2 vaccines are headache, Guillain-Barre syndrome (GBS), venous sinus thrombosis (VST), and transverse myelitis. Other neurological side effects occur in a much lower frequency. Neurological side effects occur with any of the approved vaccines but VST particularly occurs after vaccination with vector-based vaccines. Treatment of these side effects is not at variance from similar conditions due to other causes. The worst outcome of these side effects is associated with VST, why it should not be missed and treated appropriately in due time. In conclusion, safety concerns against SARS-CoV-2 vaccines are backed by an increasing number of studies reporting neurological side effects. The most frequent of them are headache, GBS, VST, and transverse myelitis. Healthcare professionals, particularly neurologists involved in the management of patients having undergone SARS-CoV-2 vaccinations, should be aware of these side effects and should stay vigilant to recognize them early and treat them adequately.

关键词： Injury to surgery interval   Secondary referral   Age   Demographic change   Neurological outcome  

摘要： Purpose To investigate the association of age with delay in spine surgery and the effects on neurological outcome after traumatic spinal cord injury (SCI). Methods Ambispective cohort study (2011-2017) in n = 213 patients consecutively enrolled in a Level I trauma center with SCI care in a metropolitan region in Germany. Age-related differences in the injury to surgery interval and conditions associated with its delay (> 12 h after SCI) were explored using age categories or continuous variables and natural cubic splines. Effects of delayed surgery or age with outcome were analyzed using multiple logistic regression. Results The median age of the study population was 58.8 years (42.0-74.6 IQR). Older age (>= 75y) was associated with a prolonged injury to surgery interval of 22.8 h (7.2-121.3) compared to 6.6 h (4.4-47.9) in younger patients (<= 44y). Main reasons for delayed surgery in older individuals were secondary referrals and multimorbidity. Shorter time span to surgery (<= 12 h) was associated with higher rates of ASIA impairment scale (AIS) conversion (OR 4.22, 95%CI 1.85-9.65), as mirrored by adjusted spline curves (< 20 h 20-25%, 20-60 h 10-20%, > 60 h < 10% probability of AIS conversion). In incomplete SCI, the probability of AIS conversion was lower in older patients [e.g., OR 0.09 (0.02-0.44) for'45-59y' vs.' <= 44y'], as confirmed by spline curves (< 40y 20-80%, >= 40y 5-20% probability). Conclusion Older patient age complexifies surgical SCI care and research. Tackling secondary referral to Level I trauma centers and delayed spine surgery imposes as tangible opportunity to improve the outcome of older SCI patients.

关键词： headache   migraine   multiple sclerosis   myasthenia gravis   pre-pregnancy counselling   pregnancy   stroke  

摘要： Neurological disease encompasses a broad spectrum of conditions which may be affected by pregnancy, present de novo in pregnancy, or are caused by the pregnancy itself. Neurological diseases remain the second most common cause of indirect maternal deaths in the UK. It is imperative that a thorough history and examination are performed when assessing pregnant women presenting with neurological conditions, and that early specialist advice is sought. Multidisciplinary team working is also integral when caring for these women. These points are highlighted with the aid of case studies, with a particular focus on epilepsy, headaches, stroke, multiple sclerosis and myasthenia gravis in pregnancy. © 2021 Elsevier Ltd