摘要： Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Hospital sickle cell clinic in Kampala and were not on disease-modifying therapy, we examined the range of MR imaging findings, and how those findings correlated with standardized demographic, clinical, neurological and neurocognitive assessments. Methods: From within a larger sample of 265 participants with HbSS ages 1-12 years not taking disease-modifying therapy and enrolled in the BRAIN SAFE study, a sub-sample of 81 underwent non-contrast MRI/MRA on a 1.5 Telsa scanner. Participants also underwent 3 standardized assessments: neurocognitive testing by experienced testers using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal z-score of -2 or lower), stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA. Participants undergoing MRI/MRA intentionally included 29 without any abnormal findings. MRI scans included T1- and T2- weighted images, T2 FLAIR and MRA three-dimensional time-of-flight technique. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist. Results: A total of 81 children with SCA were examined by MRI/MRA. Mean age was 6.48 ± 2.75 years; 50.6% were male. Mean hemoglobin was 7.26±0.90 g/dl; 75% had hemoglobin <8.0. In all, 16.7% were malnourished using standard international measures established by age and sex. Infarcts and/or arterial stenoses on MRI/MRA were detected in 42 (52%), including 13 (25%) with no other abnormalities detec

摘要： Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Inflammation is a risk factor for acute stroke. In a cross-sectional study of Ugandan children, we asked whether inflammatory markers correlated with findings on neurological and neurocognitive testing and magnetic resonance imaging (MRI). Methods: Stored plasma samples were obtained at a well study visit from 81 children, a subset within a larger sample of study participants with HbSS ages 1-12 years recruited at the Mulago Hospital sickle cell clinic in Kampala. Participants underwent 4 standardized assessments: neurocognitive testing using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal at z-score of -2 or lower), examination for prior stroke (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA, plus a non-contrast MRI/MRA on a 1.5 Telsa scanner, analyzed for T1- and T2- weighted images and T2 FLAIR. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist. Participants undergoing MRI intentionally included 29 without any abnormal findings on the three other evaluations. Plasma samples were examined for key cytokines and markers of vascular activation by a 20-plex Luminex immunoassay. Immune markers included IL1b, IL1RA, IL2, IL4, IL10, IL18, IL22, IFNg, TNFa, TNFb, sFasL, CXCL1, CXCL8 (IL8), PDGFBB, VEGFA, serpin E1 (Plasminogen Activator Inhibitor (PAI)-1), sICAM1, VCAM1, TGFa, plus assay of hsCRP. Raw immune data were transformed using Box-Cox transformations and standardized; markers with persistently skewed (non-Gaussian) distributions after transformation were dichotomized for analysis. Continuous immune variables were analyzed by repeated measures ANOVA (u

摘要： Background Immunoglobulin (IVIG) is used to treat autoimmune conditions, but there are reports of brisk hemolysis within 48 hours (hrs) of treatment due to anti-A isohemogglutinins(1). Despite these reports, hemolysis remains an unrecognized side effect of IVIG. Methods We presented a series of 3 cases of IVIG-induced hemolysis in patients with autoimmune neurological disorders. In the investigative phase, we traced the cases to a common IVIG lot number. The sample was tested to determine the anti-A titer levels. Case Studies (See Table 1) Case 1 75-year-old man presented with SOB and dysarthria from myasthenia gravis (MG). He received IVIG for 4 days. He developed a hemolytic anemia with 3 g drop in hemoglobin (Hb) 48 hours later. He needed a pRBC transfusion and folic acid. Case 2 59-year-old female with history of MG treated with IVIG at another hospital until 3 months earlier in crisis, with SOB and dysphagia. She received IVIG for 5 days and rituximab. She improved and was discharged, but returned to the ER 7 days later with SOB. Her Hb fell to 8.0 g/dL from 13 g/dL on last admission. She required a pRBC transfusion, folic acid, and vitamin B12 with improvement of SOB. Case 3 20-year-old female admitted for lower extremity weakness, diagnosed with presumed syndrome (GBS). She received IVIG for 4 days. On the 5th day, her Hb fell from 15 g/dL to 9 g/dL. She began prednisone, folic acid, and vitamin B12 with improvement in her Hb. Conclusions Although acute hemolysis is well described in the literature, it is under recognized, as exemplified by the first two cases. Their initial SOB was due to MG, so when SOB recurred, they were misdiagnosed with recurrent MG. A hemolytic anemia was later suspected, and a work up revealed a positive DAT. The initial eluate was negative against type O panel cells, suggesting a drug related hemolysis. It was only when the eluate was tested against type A cells that the etiology became clear. The third patient's hemolytic reaction w

摘要： The PLASMIC score was recently developed for rapid diagnosis of thrombotic thrombocytopenic purpura (TTP) and therapeutic decision, as ADAMTS13 is frequently unavailable. The score consists of a scale from 1 to 7 that considers clinical and laboratory factors. PLASMIC score 6 - 7, 4 - 5 and below 4 are associated with high, intermediate and low probability of ADAMTS13 deficiency, respectively. Although the PLASMIC score is validated to predict ADAMTS13 values, its role as a predictor of adverse clinical outcomes in TTP is not established. The primary aim of this study was to evaluate whether the PLASMIC score is associated with neurological complications during TTP episodes. We also evaluated the association of the score with treatment outcomes, such as number of plasma exchange procedures, need for a second line immunosuppression therapy, days in hospital and death. In the present study, we retrospectively applied the PLASMIC score at the time of diagnosis of TTP episodes treated at the UNICAMP Clinical Hospital (University of Campinas - Brazil) between 1995 and 2016. All clinical data were retrieved from medical charts. We grouped the episodes according to the PLASMIC score, calculated at diagnosis, and compared the occurrence of neurological symptoms and other clinical manifestation between the PLASMIC score groups. The association between the PLASMIC score and neurological symptoms was evaluated by regression analysis. A total of 50 episodes of TTP were identified, of these 47 episodes, and 34 patients, were included in the study. Three episodes were excluded due to lack of clinical data. Twenty-seven (79.4%) patients were women, and the mean age was 35.7 years (SD 12.7). At the diagnosis, the mean PLASMIC score was 6, no PLASMIC score below 4 was detected, and the most common clinical features were thrombocytopenia (mean platelet count = 21,029 x 109 / L [SD 18,371 x 109]) and reticulocytosis (mean count = 7.83% [SD 5.29]). Plasma exchange was the main treatmen

摘要： Nilotinib is a tyrosine kinase inhibitor used to treat patients with chronic myeloid leukemia (CML). This agent is also being studied in neurodegenerative disorders including Parkinson disease. Studies have shown that nilotinib may decrease the accumulation of parkin substrates and decrease the loss of dopaminergic cells. The use of nilotinib in neurologic disorders is relatively new, and little information about this use has been published. We report on a patient receiving nilotinib for CML. The patient had no previous neurologic deficits, and developed intermittent dystonic posturing of the left upper extremity and cognitive impairment after she began nilotinib treatment. The mechanisms behind this adverse effect are not clear;however, her symptoms began after nilotinib was introduced, decreased with dose reduction, stopped with its cessation, and re-emerged when the medication was restarted. To our knowledge, this is the first reported patient with neurologic symptoms secondary to nilotinib use.

关键词： GOSR2   Membrin   Golgi   secretory pathway   progressive myoclonus epilepsy  

摘要： Successive fusion events between transport vesicles and their target membranes mediate trafficking of secreted, membrane- and organelle-localised proteins. During the initial steps of this process, termed the secretory pathway, COPII vesicles bud from the endoplasmic reticulum (ER) and fuse with the cis-Golgi membrane, thus depositing their cargo. This fusion step is driven by a quartet of SNARE proteins that includes the cis-Golgi t-SNARE Membrin, encoded by the GOSR2 gene. Mis-sense mutations in GOSR2 result in Progressive Myoclonus Epilepsy (PME), a severe neurological disorder characterised by ataxia, myoclonus and seizures in the absence of significant cognitive impairment. However, given the ubiquitous and essential function of ER-to-Golgi transport, why GOSR2 mutations cause neurological dysfunction and not lethality or a broader range of developmental defects has remained an enigma. Here we highlight new work that has shed light on this issue and incorporate insights into canonical and non-canonical secretory trafficking pathways in neurons to speculate as to the cellular and molecular mechanisms underlying GOSR2 PME. This article is part of a Special Issue entitled: SNARE proteins: a long journey of science in brain physiology and pathology: from molecular. (C) 2019 Published by Elsevier Ltd. on behalf of IBRO.

关键词： Community based   patient centered   process quality   self-efficacy   self-management   service redesign  

摘要： Objectives: The objective of this study is to identify patient reported experiences of using community rehabilitation and/or support services whilst living with a long-term neurological condition, and perceptions of their impact on quality of life. Methods: Nine electronic databases were searched for peer-reviewed qualitative studies from 2005 to 2016, which met the inclusion criteria. Critical appraisal, data extraction, and quality assessment of 37 included papers were performed by three reviewers. One hundred and one findings were extracted. Meta-aggregation was used to synthesize findings. Findings: Seven ?synthesized findings? [SF] were produced: Interactions with some professionals provide active participation, choice, confidence and autonomy [SF1];Interactions with some professionals are disempowering and depersonalized [SF2];Effective communication, specialist knowledge and an individualized approach to information provision is needed [SF3];Indicators of success vary and may not be clear [SF4];Informal support from family/friends is valued [SF5];Opportunities for peer support/social interaction is valued [SF6];Coordination required to ensure continuity during transition to community [SF7]. Conclusion: Patient reported experiences identified common factors associated with process quality (respect, choice, autonomy, information provision, communication) and activities of patient centered care (personalized care, shared decision-making, self-management support) despite heterogeneity of neurological conditions, service configurations, and geographical location. These factors impact quality of life.

关键词： Stroke   Triiodothyronineis   Prognosis   Bioinformatics analysis  

摘要： Backgroud Patients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear. Methods We retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed. Results FT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI)

关键词： Functional neurological disorders   Conversion disorders   Dissociative disorders   SPECT  

摘要： Background In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a "psychodynamic" lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder. Case presentation Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology. Conclusions This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of "dynamic lesion".

关键词： 思维导图   PBL   教学模式   神经病学   规培医生   教学质量   住院医师规范化培训  

摘要： 目的探讨基于思维导图的PBL教学模式在神经病学规培医师中应用的可行性及有效性。方法将2017年9月—2018年9月于西安交通大学第二附属医院神经内科规培的医师125名进行随机分为传统教学组及基于思维导图的PBL教学组,教学结束后分别进行课程满意度调查及临床考核,比较两组规培医师的满意度及考核成绩。结果基于思维导图的PBL教学组对思维导图结合PBL教学法评价较好,超过90%的规培医师认为有利于知识巩固,提高检索能力,构建知识体系(P<0.05);临床考核方面:基于思维导图的PBL教学组从理论成绩、操作成绩及病例分析均优于传统教学组,差异具有统计学意义(P<0.05)。结论基于思维导图的PBL教学方法有利于知识巩固,提高检索能力,构建知识体系,在教学效果上更胜一筹,更符合当前的教育理念,更符合应用型人才的培养。