关键词： MCAO   BMSCs   PI3K   AKT   CRMP-2   GAP-43   Axon growth  

摘要： Background: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. However, the underlying protective mechanism remains undetermined. Here, we tested the hypothesis that transplantation of BMSCs via intravenous injection can alleviate neurological functional deficits through activating PI3K/AKT signaling pathway after cerebral ischemia in rats. Methods: A cerebral ischemic rat model was established by the 2 h middle cerebral artery occlusion (MCAO). Twenty-four hours later, BMSCs (1 x 10(6) in 1 ml PBS) from SD rats were injected into the tail vein. Neurological function was evaluated by modified neurological severity score (mNSS) and modified adhesive removal test before and on d1, d3, d7, d10 and d14 after MCAO. Protein expressions of AKT, GSK-3 beta, CRMP-2 and GAP-43 were detected by Western-bolt. NF-200 was detected by immunofluorescence. Results: BMSCs transplantation did not only significantly improve the mNSS score and the adhesive-removal somatosensory test after MCAO, but also increase the density of NF-200 and the expression of p-AKT, pGSK-3 beta and GAP-43, while decrease the expression of pCRMP-2. Meanwhile, these effects can be suppressed by LY294002, a specific inhibitor of PI3K/AKT. Conclusion: These data suggest that transplantation of BMSCs could promote axon growth and neurological deficit recovery after MCAO, which was associated with activation of PI3K/AKT /GSK-3 beta/CRMP-2 signaling pathway.

关键词： ABCC8   congenital hyperinsulinism   diazoxide   epilepsy   pancreatectomy  

摘要： Aim Congenital hyperinsulinism (CHI) is a heterogeneous disease with variable genetic etiology, histopathology, and clinical phenotype. This study aims to describe the clinical characteristics of persistent CHI and evaluate long-term neurological outcome and its risk factors in a cohort of Egyptian children. Methods Clinical, genetic, and biochemical data of 42 patients with CHI were collected. Patients were invited for neurological assessment, electroencephalogram, and magnetic resonance imaging of the brain. Results ABCC8 mutation was found in (61%) of cases who underwent genetic testing (17/28). Five cases with homozygous biparental ABCC8 mutation responded to combined diazoxide and octreotide without needing surgery. Seven out of twenty-one patients who had pancreatectomy (33%) developed diabetes after a median period of 4.8 (range:1-10) years following surgery. Fifty-five percent of our patients had neurodevelopmental impairment at follow-up. Logistic regression analysis has shown that delayed referral to tertiary centre for more than 8 days, delayed diagnosis of CHI for more than 14 days and hospital admission for more than 30 days, are significant predictors of unfavorable neurological sequelae in CHI;(OR = 12.7 [2.56], p = 0.001), (OR = 12.7 [2.9-56], p = 0.001), and (OR = 3.8 [0.14.5], p = 0.043), respectively. Conclusions ABCC8 mutation was the commonest genetic mutation underlying CHI in this study group. CHI cases with biparental homozygous ABCC8 mutation may show response to combined octreotide and diazoxide therapy. More than half of our patients had neurodevelopmental impairment at follow-up. Delayed referral to expert centre, delayed diagnosis and longer hospital stay are significant predictors of neurological disability in CHI cases.

关键词： Protocadherin 19   PCDH19   PCDH19-Clustering Epilepsy (PCDH19-CE)   Epilepsy   Synapses  

摘要： PCDH19-Clustering Epilepsy (PCDH19-CE) is an infantile onset disorder caused by mutation of the X-linked PCDH19 gene. Intriguingly, heterozygous females are affected while hemizygous males are not. While there is compelling evidence that this disorder stems from the coexistence of WT and PCDH19-null cells, the cellular mechanism underpinning the neurological phenotype remains unclear. Here, we investigate the impact of Pcdh19 WT and KO neuron mosaicism on synaptogenesis and network activity. Using our previously established knock-in and knock-out mouse models, together with CRISPR-Cas9 genome editing technology, we demonstrate a reduction in excitatory synaptic contacts between PCDH19-expressing and PCDH19-null neurons. Significantly altered neuronal morphology and neuronal network activities were also identified in the mixed populations. In addition, we show that in Pcdh19 heterozygous mice, where the coexistence of WT and KO neurons naturally occurs, aberrant contralateral axonal branching is present. Overall, our data show that mosaic expression of PCDH19 disrupts physiological neurite communication leading to abnormal neuronal activity, a hallmark of PCDH19-CE.

关键词： COVID-19   neurological   presentation   SARS-CoV-2   symptom  

摘要： Objective To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea. Methods We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without. Demographic, clinical symptoms, laboratory result, and clinical outcomes were collected. Results Out of 282 patients who had neurology consult during this period, we identified 56 (mean age 69.2 years, 57% women) who tested COVID-19-positive and had neurologic symptoms on initial presentation. Of these, 23 patients (mean age 65.2 years, 52% women) had no typical COVID-19 symptoms while 33 did (mean age 72.2 years, 60% woman). In both groups, impaired consciousness was the most common initial neurologic symptom, followed by stroke, unsteady gait, headache, seizure, syncopal event, acute vision changes, and intracranial hemorrhage. Out of the 23 patients without typical COVID-19 symptoms on presentation, 10 went on to develop typical symptoms with 8 needing supplemental oxygen and one requiring mechanical ventilation. Conclusion Patients who have COVID-19 can present with serious neurologic symptoms such as impaired consciousness and stroke even without typical COVID-19 symptoms. Those without typical COVID-19 symptoms can later develop typical symptoms severe enough to need respiratory support.

摘要： We surveyed neurologists who completed a global health experience as residents or fellows to assess the impact of the experience. A total of 100% (n = 72) would recommend the experience to others. Most reported improved clinical (86%) and examination (82%) skills. All gained an understanding of different health care systems, and 83% reported deeper commitment to underserved populations. A total of 41 participants (57%) reported more judicious use of resources upon return to the United States. Global health electives had a positive impact on neurology trainees. More attention to the host country perspective and predeparture training may help inform program structure and participant expectations in the future. ANN NEUROL 2021

关键词： functional dystonia   functional neurological disorders   functional tremor   functional weakness   neurological diseases   organic  

摘要： Background and purpose The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs"). Methods For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables). Results Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities. Conclusions Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.

关键词： adverse events   child   complications   general anesthesia   infant   morbidity  

摘要： Background Perianesthetic neurological adverse events are rare in children and have been studied in detail in the settings of cardiac surgery and regional anesthesia. Our study aims to characterize perianesthetic neurological adverse events in children in the setting of all types of surgery and diagnostic or interventional procedures, to evaluate anesthesia's role, and to identify factors amenable to prevention. Methods We conducted a retrospective study by reviewing all the anesthetic encounters reported in the Wake-Up Safe database between January 2010 and December 2017. Results The rate of perianesthetic neurological adverse events was 0.49 per 10 000 pediatric anesthetic encounters. The odds of NAE were significantly higher in children who were older than 6 months;had American Society of Anesthesiologists physical status (ASA PS) of 3, 4, or 5;or had American Society of Anesthesiologists Emergency (ASA E) status. Seizures were the most common NAE. Overall, 23 (18.1%) children with neurological adverse events died, and 33 (26%) experienced permanent or severe permanent harm. The risk of death was higher in infants and in children with ASA PS of 3, 4, or 5;ASA E status;preexisting neurological abnormality;or preexisting neurological deficit and in events associated with cardiac arrest or trauma. Anesthesia contributed to 24 (18.9%) events;patient disease was the primary causative factor in 95 (74.8%) adverse events, and 37 (29.1%) events were preventable, including 2 deaths. Preventable factors broadly included inadequate preoptimization, complications during airway management and central venous catheter placement, and suboptimal patient positioning. Conclusion Perianesthetic neurological adverse events are rare in children and have a poor outcome. Our study has described pediatric perianesthetic neurological injury in detail and identified contributing factors that can be optimized during various phases of perianesthetic care. This information can be utilized dur

关键词： Microglia   Epigenetics   Histone modifications   DNA methylation   Innate immune memory   Neurological disease  

摘要： Microglia are myeloid-derived cells recognized as brain-resident macrophages. They act as the first and main line of immune defense in the central nervous system (CNS). Microglia have high phenotypic plasticity and are essential for regulating healthy brain homeostasis, and their dysregulation underlies the onset and progression of several CNS pathologies through impaired inflammatory responses. Aberrant microglial activation, following an inflammatory insult, is associated with epigenetic dysregulation in various CNS pathologies. Emerging data suggest that certain stimuli to myeloid cells determine enhanced or attenuated responses to subsequent stimuli. These phenomena, generally termed innate immune memory (IIM), are highly dependent on epigenetic reprogramming. Microglial priming has been reported in several neurological diseases and corresponds to a state of increased permissiveness or exacerbated response, promoted by continuous exposure to a chronic proinflammatory environment. In this article, we provide extensive evidence of these epigenetic-mediated phenomena under neurological conditions and discuss their contribution to pathogenesis and their clinical implications, including those concerning potential novel therapeutic approaches.

摘要： Background Literature regarding congenital subependymal giant cell astrocytomas (SEGA) is limited, and suggests they are at risk of rapid growth and complications. We sought to characterise the growth patterns of congenital SEGA. The second part of the study was an exploratory analysis of congenital SEGA as a possible biomarker for poor neurological outcome. Methods This single-centre case series describes ten patients with TSC who had SEGA diagnosed before 12 months. SEGA diameter and volumetric growth were analysed using serial MRIs. Neurological outcomes were compared to a genotype-matched group. Results All children with congenital SEGA had aTSC2mutation. Patients were followed for 1-8.7 years, during which median SEGA growth rate was 1.1 mm/yr in diameter or 150 mm(3)/yr volumetrically. SEGA with volume > 500 mm(3)had a significantly higher growth rate compared with smaller SEGA (462 mm(3)/yr vs. 42 mm(3)/yr,p = 0.0095). Children with congenital SEGA had a high prevalence of severe epilepsy, developmental disability and autism spectrum disorder. Conclusion Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature. Frequent neuroimaging surveillance is recommended for congenital SEGA with volumes exceeding 500 mm(3). Impact Congenital SEGA occur in 9.2% of paediatric patients with tuberous sclerosis complex. There are few published cases of congenital SEGA to date. This case series of ten patients adds our experience seen in a tertiary referral hospital over 10 years. Congenital SEGA can follow a relatively benign course with a lower growth rate compared with published literature. Congenital SEGA with volume exceeding 500 mm3 had a significantly higher growth rate compared with smaller SEGA and should have more frequent neuroimaging surveillance.

关键词： Thrombotic thrombocytopenic purpura   Hemolytic uremic syndrome   Encephalopathy   Seizures   Posterior reversible encephalopathy syndrome (PRES)  

摘要： The objective of this study was to compare the frequency and severity of neurologic manifestations in adult patients diagnosed with thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and atypical HUS (aHUS). This is a retrospective cohort study of adult patients diagnosed with TTP, HUS and atypical HUS hospitalized at a tertiary center between January 2004 and October 2016. A total of 42 TTP, 16 HUS and 20 aHUS episodes were reviewed to collect clinical, laboratory and radiographic data, as well as information regarding long-term functional outcome. Neurologic symptoms are more common in patients with TTP and HUS as compared to aHUS (p < 0.001 and p = 0.002, respectively). Encephalopathy occurred in 29 TTP (69%) and 11 HUS (68%) episodes. Focal deficits were only observed in patients with TTP (n = 8 [19%]). Seizures were most commonly seen in HUS patients (n = 8 [50%]). Posterior reversible encephalopathy syndrome (PRES) was the most common neuroimaging finding in these syndromes;ischemic infarcts and hemorrhages occurred uncommonly. There was no correlation between presence of neurologic symptoms or neuroimaging abnormalities and poor outcome. Patients with TTP and HUS appear to have a similar spectrum of neurologic manifestations, whereas neurologic involvement is less common in aHUS. PRES is the most common imaging abnormality, and may present atypically. Despite presence of neurologic symptoms or neuroimaging abnormalities, patients with thrombotic microangiopathy (TMA) tend to have favorable long-term outcomes.