关键词： Amyotrophic lateral sclerosis   ERK-1   2   Demyelination   Neurodegeneration   Neuroinflammation  

摘要： Cell signal transduction pathways are essential modulators of several physiological and pathological processes in the brain. During overactivation, these signaling processes may lead to disease progression. Abnormal protein kinase activation is associated with several biological dysfunctions that facilitate neurodegeneration under different biological conditions. As a result, these signaling pathways are essential in understanding brain disorders' development or progression. Recent research findings indicate the crucial role of extracellular signal regulated kinase-1/2 (ERK-1/2) signaling during the neuronal development process. ERK-1/2 is a key component of its mitogen-activated protein kinase (MAPK) group, controlling certain neurological activities by regulating metabolic pathways, cell proliferation, differentiation, and apoptosis. ERK-1/2 also influences neuronal elastic properties, nerve growth, and neurological and cognitive processing during brain injuries. The primary goal of this review is to elucidate the activation of ERK1/2 signaling, which is involved in the development of several ALS-related neuropathological dysfunctions. ALS is a rare neurological disorder category that mainly affects the nerve cells responsible for regulating voluntary muscle activity. ALS is progressive, which means that the symptoms are getting worse over time, and there is no cure for ALS and no effective treatment to avoid or reverse. Genetic abnormalities, oligodendrocyte degradation, glial overactivation, and immune deregulation are associated with ALS progression. Furthermore, the current review also identifies ERK-1/2 signaling inhibitors that can promote neuroprotection and neurotrophic effects against the clinical-pathological presentation of ALS. As a result, in the future, the potential ERK-1/2 signaling inhibitors could be used in the treatment of ALS and related neurocomplications.

关键词：     Subarachnoid hemorrhage   Endovascular   Perforation   Cerebral blood flow  

摘要： Objective: Cerebral Blood Flow (CBF) change after Subarachnoid Hemorrhage (SAH) is strongly associated with brain injuries such as early brain injury and delayed cerebral ischemia. We evaluated the correlation between CBF using Laser Speckle Flow Imaging (LSFI) after SAH and neurological findings in the sub-acute phase. Method: An SAH was induced by endovascular perforation in male mice. CBF was quantitatively measured by using LSFI at six time points, immediately to 14 days after SAH induction. Behavior tests and survival rate were evaluated. The mice were divided into recovery and hypo-perfusion groups according to their CBF at 1 day after the procedure. Result: Forty mice were included in this study. Five mice (20%) were included in the hypo-perfusion group, and the remaining 20 (80%) mice were classified as the recovery group. The decrease of CBF in the recovery group was observed until 1 day after the procedure. However, the decrease of CBF in the hypo-perfusion group was prolonged until 7 days after the procedure. Neurological findings and survival rates in the hypo-perfusion group were significantly worse than those in the recovery group. The low alternation cases (< 50%) in the Y maze test in the recovery group (n = 5) had significantly lower CBF at 1 day after the procedure. Conclusion: Low blood flow at 1 day after SAH was associated with worse survival rate, neurological findings, and memory disturbance. Early improvement in CBF may be associated with an improved prognosis after SAH.

关键词： Fatigue   Neurological Fatigue Index   outcome assessment   reliability and validity   stroke  

摘要： Objective: To test the psychometric properties of a Chinese version of the Neurological Fatigue Index-Stroke (C-NFI-Stroke) in stroke survivors. Design: This was a validation study. Cross-cultural adaptation of the scale was conducted according to standard guidelines. Reliability, validity, responsiveness, and interpretability were measured. Setting: Self-help groups and a community center. Subjects: One hundred and twelve Chinese stroke survivors and 65 healthy Chinese older people living in the community. Interventions: Not applicable. Main measures: The C-NFI-Stroke, Fatigue Severity Scale, Mental Fatigue Scale, General Self-Efficacy Scale, and Geriatric Depression Scale were used. Results: Cronbach's alpha coefficients were 0.69-0.88;the item-level agreement was 70.4%-88.9%;the weighted Kappa value was 0.47-0.79;and the intra-class correlation coefficients were 0.88-0.93. The C-NFI-Stroke had no ceiling and floor effects. It had good content validity and had two factors, "lack of energy" and "tiredness/weakness." The confirmatory factor analysis showed a good fit to the model. The C-NFI-Stroke significantly correlated with existing fatigue scales (r(s) = 0.55-0.63), self-efficacy (r(s) = -0.31 to -0.37), and depressive symptoms (r(s) = 0.53-0.60). The C-NFI-Stroke could discern differences between stroke survivors and healthy older people. Conclusions: The C-NFI-Stroke is a reliable and valid tool for clinical and research use on people who have been diagnosed with stroke for a year or more, although its factor structure differs from that of the original English version.

关键词： Alzheimer's disease   Genetics of the nervous system   Predictive markers  

摘要： Yang et al. generated a genomic atlas of protein levels in brain, cerebrospinal fluid and plasma and used human genetics approaches to identify proteins implicated in neurological diseases as well as druggable targets. Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer's disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer's disease, Parkinson's disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases.

关键词： aortic arch   aortic dissection   arch repair   frozen elephant trunk   spinal cord ischemia   stroke  

关键词： early motor rehabilitation   ischaemic stroke   neurorehabilitation  

摘要： Background and purpose Early pharmacological support for post-stroke neurorehabilitation has seen an abundance of mixed results from clinical trials, leaving practitioners at a loss regarding the best options to improve patient outcomes. The objective of this evidence-based guideline is to support clinical decision-making of healthcare professionals involved in the recovery of stroke survivors. Methods This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. PubMed, Cochrane Library and Embase were searched (from database inception to June 2018, inclusive) to identify studies on pharmacological interventions for stroke rehabilitation initiated in the first 7 days (inclusive) after stroke, which were delivered together with neurorehabilitation. A sensitivity analysis was conducted on identified interventions to address results from breaking studies (from end of search to February 2020). Results Upon manually screening 17,969 unique database entries (of 57,001 original query results), interventions underwent meta-analysis. Cerebrolysin (30 ml/day, intravenous, minimum 10 days) and citalopram (20 mg/day, oral) are recommended for clinical use for early neurorehabilitation after acute ischaemic stroke. The remaining interventions identified by our systematic search are not recommended for clinical use: amphetamine (5, 10 mg/day, oral), citalopram (10 mg/day, oral), dextroamphetamine (10 mg/day, oral), Di-Huang-Yi-Zhi (2 x 18 g/day, oral), fluoxetine (20 mg/day, oral), lithium (2 x 300 mg/day, oral), MLC601(3 x 400 mg/day, oral), phosphodiesterase-5 inhibitor PF-03049423 (6 mg/day, oral). No recommendation 'for' or 'against' is provided for selegiline (5 mg/day, oral). Issues with safety and tolerability were identified for amphetamine, dextroamphetamine, fluoxetine and lithium. Conclusions This guideline provides information for clinicians regarding existing pharmacological support in interventions for

关键词： Pneumology/Respiratory System   Otorhinolaryngology   Dentistry   Neurology   Internal Medicine   Pediatrics  

关键词： Parry-Romberg syndrome   Hemifacial atrophy   Midline indentation   White matter lesions  

摘要： In this report, we describe an unusual case of progressive hemifacial atrophy or Parry-Romberg syndrome in a 10-year-old girl with progressive hemifacial microsomia and limb anomalies who had brain magnetic resonance imaging (MRI) findings of white matter hyper-intensities. Patients typically present with neurological manifestations such as epilepsy, facial pain, and migraines and ophthalmological symptoms in conjunction with white matter lesions. The patient demonstrated normal cognition and psychomotor development despite the presence of white matter lesions in her frontal lobe that is commonly associated with neurological symptoms. This report brings attention to the complicated relationship between facial, limb and brain imaging findings in ParryRomberg syndrome and differentiates it from hemifacial microsomia syndrome.

关键词： Elderly patients   Comorbidities   Intracranial meningiomas   Operative risks   Meningioma surgery   Neurological conditions  

摘要： Introduction While surgery is the primary treatment choice for intracranial meningiomas in young patients, surgery in elderly patients, especially those with pre-existing comorbidities, has been the subject of repeated discussion. This study investigated the postoperative risks and neurological benefits of meningioma surgery in elderly patients compared to young patients. Methods In total, 768 patients were included and divided into two main groups: group I (age: <= 64 years;484 young patients) and group II (age: >= 65 years;284 elderly patients). Group II was subdivided into: IIa (age: 65-69 years), IIb (age: 70-79 years);and IIc (age: >= 80 years). Results The total tumor resection rate was higher in the elderly cohort than in the young cohort (84.5 and 76.2%, respectively). 154 young patients (31.8%) and 132 elderly patients (46.5%) developed postoperative morbidities, with the three most common being bleeding (12.9%), cranial nerve disorder (10%) and CSF fistula (8.1%). Postoperative bleeding, palsy, speech disorder, pneumonia and renal insufficiency were dependent on age (r = 0.123, p = 0.001;r = 0.089, p = 0.014;r = 0.100, p = 0.006;r = 0.098, p = 0.007 and r = 0.084, p = 0.020) and presented more often in elderly patients. 6 young and 15 elderly patients died during the 17.4-year observation period. Most patients showed a significant improvement in postoperative KPS (p < 0.001), except those over 80 years old (p = 0.753). The KPS at the last follow-up was significantly improved in all patients (p < 0.001). Conclusion Meningioma surgery is associated with a higher rate of postoperative complications in elderly patients than in young patients. Most elderly patients, similar to young patients, show a significant improvement in neurological status postoperatively.

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摘要： There is growing recognition that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can lead to both acute and long-term neurological sequelae [1]. In addition to the neurological consequences of severe illness in itself, proposed mechanisms of SARS-CoV-2-associated neurological complications include direct neuroinvasion, and indirect mechanisms, of vascular and inflammatory/autoimmune origin (Fig. 1). The identification and diagnosis of these neurological complications are challenging, particularly in the context of overstrained medical systems, where an under-recognition of neurological manifestations may contribute to an increase in acute and long-term complications and poor outcomes. In addition, there is a high incidence of general critical care complications, for example, hypoxia, metabolic derangements, general inflammation, and drug toxicity/side effects, which can make proper attribution to coronavirus disease 2019 (COVID-19) difficult. We discuss the neurological complications associated with COVID-19 (NeuroCOVID) for general intensivists with an emphasis on key symptoms and signs to look for which may change management and/or provide a potential avenue for targeted therapies to improve outcomes.