关键词： Stroke   ischemic stroke   sleep apnea   sleep breathing disorder   early neurological deterioration  

摘要： Background and purpose: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients. Methods: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission. Results: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI >= 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI >= 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024;95% confidence interval 1.006 to 1.042;P = .008). Conclusions: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END.

摘要： Research into the role of the gut microbiome in modulating brain function has rapidly increased over the past 10 years, albeit chiefly in animal models. Increasing dinical and preclinical evidence implicates the microbiome as a possible key susceptibility factor for neurological disorders, including Alzheimer's disease, autism spectrum disorder, multiple sclerosis, Parkinson's disease, and stroke. Cross-sectional dinical studies are bolstering the concept of altered microbial composition contributing to the pathophysiology of such diseases. However, the field is nascent, and interpretation of such data is often difficult given that the composition of the microbiome is influenced by various factors such as diet and exercise. Longitudinal studies and randomised controlled trials in humans are needed to find out if targeting the microbiome can yield novel therapeutic strategies. Systems biology approaches will also be important in integrating such data with genomic and metabolomic datasets from clinical cohorts with neurological disease to help guide individual treatment selection.

关键词： Uganda   Neurological illness   Neurological infections   Stroke   Head trauma   Global neurology  

摘要： Background While the burden of neurologic illness in developing countries is increasing, less is known about mortality among patients admitted to sub-Saharan African hospitals with neurologic disease. We sought to characterize the rate and patient-level predictors of in-hospital mortality in a Ugandan Neurology ***. Methods Data was prospectively collected on 335 patients admitted to the Neurology ward of Mulago Hospital, Kampala, Uganda. Kaplan-Meier survival curves and multivariate COX proportional hazard modeling were used to assess survival. Results Within our sample (n = 307), 35.8% received no diagnosis at time of hospital admission. Stroke (27.3%), head trauma (19.6%), and malaria (16.0%) were the most common diagnoses. Among the 56 (18.5%) patients who died during the index hospitalization, the most common diagnosis at admission and at death was stroke. Adjusted regression analysis showed that patients without a diagnosis at time of death (HR = 7.01 [2.42-20.35], p < .001) and those with diagnoses of infections (HR = 5.21 [2.16-12.58], p = <.001), stroke (HR = 2.69 [1.20-6.04], p = .017), or head trauma (HR = 3.39, [1.27-9.07], p = 0.15) had worse survival. Conclusions In-hospital mortality affected nearly 20% of the cohort, with worse survival among those without a diagnosis and with infections, stroke, head trauma. Future work should identify reasons for increased mortality among these high-risk groups and implement targeted interventions.

关键词： Carbon monoxide poisoning   delayed neurological sequelae   Tau protein   TDZD-8   GSK-3 beta  

摘要： Objective: Acute carbon monoxide (CO?poisoning can cause delayed neurological sequelae (DNS). Glycogen synthase kinase 3 beta (GSK-3 beta) /Tau protein pathway is reported to play a key role in neurological abnormalities. In the present study, we aimed to determine the role of GSK-3 beta/Tau in DNS following acute CO poisoning. Methods: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a specific non-competitive inhibitor of GSK-3 beta, was used to inhibit GSK-3 beta. Twenty-four male Sprague-Dawley rats were randomly assigned to the three groups: Control group, CO group and CO-TDZD-8 group. Rats breathed 1000 ppm CO for 40 minutes and then 3000 ppm for up to 20 minutes until they lost consciousness. TDZD-8 (1 mg/kg) was administered intravenously three times after the end of CO exposure at 0, 24, 48 hours late. Learning and memory abilities were observed using the Morris Water Maze (MWM). Brain histological changes were evaluated by hematoxylin-eosin staining. Moreover, the expression levels of Tau and GSK-3 beta were detected after acute carbon monoxide poisoning. Results: TDZD-8 significantly attenuated the learning and memory dysfunction induced by acute CO poisoning, ameliorated the histology structure of damaged neural cells in cortex and hippocampus CA1 area. TDZD-8 clearly decreased p-Tau expression, reversed the reduction of p-GSK-3 beta induced by acute CO poisoning. Conclusions: The therapeutic effect of TDZD-8 in alleviating DNS caused by acute CO poisoning is related to the inactivation of Tau by intensifying the level of GSK-3 beta phosphorylation.

关键词： Functional Neurology   Chiropractic   Critical review   Evidence   Effect   Benefit  

摘要： Background Functional Neurology (FN), founded by FR Carrick, is an approach used by some chiropractors to treat a multitude of conditions via the nervous system including the brain. However, it seems to lack easily obtainable scientific evidence for its clinical validity. Objectives 1) To define the topics of FR Carrick's publications, 2) to define the proportion of articles that are research studies, case studies, abstracts and conference papers, 3) to define how many of these are clinical research studies that purported or appeared to deal with the effect or benefit of FN, 4) in these studies, to establish whether the design and overall study method were suitable for research into the effect or benefit of FN, and 5) to describe the evidence available in relation to the clinical effect or benefit of FN, taking into account seven minimal methodological criteria. Method A literature search was done on Pubmed from its inception till October 2018, supplemented by a search on Scopus and ResearchGate to find all published documents by FR Carrick. We identified their types and topics, retaining for a critical review full text scientific articles appearing to test effect/benefit of FN procedures, subjecting them to a basic quality assessment (scoring 0-7). Results from studies of methodologically acceptable standard would be taken into account. Results We found 121 published texts, 39 of which were full scientific research articles. Of these, 23 dealt with topics relating to FN. Fourteen articles reported on clinical validity but only seven included a control group. The methodological quality of these seven articles was low, ranging between 1.5-4 out of 7. We therefore did not further report the outcomes of these studies. Conclusion We found no acceptable evidence in favour of effect/benefit of the FN approach. We therefore do not recommend its promotion as an evidence-based method. Further research on this topic should be conducted in collaboration with independent scient

摘要： A functional neurologic disorder is a prevalent and disabling condition at the intersection of neurology and psychiatry [1] with a current PubMed search of the term Functional Neurology (FN) listing 44,939 articles [2], 2618 Systematic Reviews [3] and 191 Meta-Analysis [4]. A PubMed search of my name and FN finds one publication addressing persistent vegetative state as a pejorative term [5] and another addressing the metrological performance of instruments used in clinical evaluation of balance [6]. However, Demortier and Leboeuf-Yde reviewed 121 of my publications through October, 2018 to measure the effect/benefit of treatment/intervention using a FN approach when I have not written anything on the subject.

关键词： Robotic gait training   Rehabilitation   Gait   Stroke   Spinal cord injury   Assist-as-needed  

摘要： Background In clinical practice, therapists choose the amount of assistance for robot-assisted training. This can result in outcomes that are influenced by subjective decisions and tuning of training parameters can be time-consuming. Therefore, various algorithms to automatically tune the assistance have been developed. However, the assistance applied by these algorithms has not been directly compared to manually-tuned assistance yet. In this study, we focused on subtask-based assistance and compared automatically-tuned (AT) robotic assistance with manually-tuned (MT) robotic assistance. Methods Ten people with neurological disorders (six stroke, four spinal cord injury) walked in the LOPES II gait trainer with AT and MT assistance. In both cases, assistance was adjusted separately for various subtasks of walking (in this study defined as control of: weight shift, lateral foot placement, trailing and leading limb angle, prepositioning, stability during stance, foot clearance). For the MT approach, robotic assistance was tuned by an experienced therapist and for the AT approach an algorithm that adjusted the assistance based on performances for the different subtasks was used. Time needed to tune the assistance, assistance levels and deviations from reference trajectories were compared between both approaches. In addition, participants evaluated safety, comfort, effect and amount of assistance for the AT and MT approach. Results For the AT algorithm, stable assistance levels were reached quicker than for the MT approach. Considerable differences in the assistance per subtask provided by the two approaches were found. The amount of assistance was more often higher for the MT approach than for the AT approach. Despite this, the largest deviations from the reference trajectories were found for the MT algorithm. Participants did not clearly prefer one approach over the other regarding safety, comfort, effect and amount of assistance. Conclusion Automatic tuning had the f

关键词： Combined malonic and methylmalonic aciduria   ACSF3   mtFASII   Metabolic flexibility   Brain energy metabolism  

摘要： Combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism which has been proposed being a benign condition. However, older patients may present with neurological manifestations such as seizures, memory problems, psychiatric problems and/ or cognitive decline. In fibroblasts from CMAMMA patients we have recently demonstrated a dysregulation of energy metabolism with increased dependency on beta-oxidation for energy production. Because of the inability of the brain to rely efficiently on this pathway to retrieve the required energy to a great extent, we hypothesize an alternative disease-causing mechanism that does not only include the accumulation of the metabolites malonic and methylmalonic acids. Here, we suggest a novel hypothesis on the possible pathophysiological mechanism responsible for the development of neurological symptoms in the long-run.

关键词： ubiquitination   ubiquitin ligases   seizure   epilepsy   degradation   proteasome  

摘要： Ubiquitination is a post-translational modification that can dynamically alter the function, degradation and transport of a protein, as well as its interaction with other proteins, and activity of an enzyme. Dysfunctional ubiquitination is detrimental to normal cellular functions, and can result in severe diseases. Over the last decade, although much research has focused on deciphering the role of the ubiquitination/ubiquitin proteasome system (UPS) in the onset and progression of various neurological disorders, the specific relationship between ubiquitination and various epilepsies has not been carefully reviewed. As an increasing amount of research has revealed the roles of ubiquitination in the trafficking of ion channels and the turn-over of synaptic receptors, it is crucial to take a deeper look into ubiquitination-associated epilepsy. Here, we review the role of ubiquitination in maintaining normal cellular activities in neurons and recent findings on the dysregulation of ubiquitination in epilepsy. We particularly focus on rare neurological disorders with comorbid epilepsy in the hope of drawing more attention to this area. Through categorizing epilepsy-associated E3 ubiquitin ligases and their substrates and discussing ubiquitination-related rare neurological disorders, we summarize where the field stands at the moment and what directions we should consider in the future. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

关键词： ABNS   Education   Residency education   USMLE step 2  

摘要： Objectives: The neurosurgery residency match is becoming increasingly competitive, with numerous factors being considered as part of the application. We aim to determine whether USMLE Step 2 scores were a significant predictor of neurosurgery board performance. Patients and methods: Residents who entered a neurological surgery residency program at a single academic institution during 2000-2017 provided scores for all ABNS attempts, USMLE Step 1 and Step 2 scores. Data were deidentified and analyzed for correlation and regression. Pearson's correlation coefficients were determined. Results: USMLE Step 1, Step 2, and maximum ABNS scores were all normally distributed. Step 1 and Step 2 scores were less variable than ABNS scores. USMLE Step 2 and residents' best ABNS written examination scores were not correlated (Pearson Correlation of 0.228 with a 2-tailed significance of 0.272). No outliers were present. When comparing USMLE Step 2 scores with year in residency at which residents scored over 300 on the ABNS written examination, Pearson correlation was -0.500 (p = .015). A simple linear regression was calculated using Step 2 scores to predict the passing year of ABNS written examination (F(1,14) = 6.984, p = .015, R-2 = 0.25). Conclusion: Although other studies have found correlations between USMLE Step 2 scores and performance before graduating medical school and during residency for other specialties, this is the first study comparing USMLE Step 2 scores with the ABNS written examination scores of neurosurgical residents. Our data showed that USMLE Step 2 was not a reliable predictor of ABNS written examination scores.