关键词： Achillea biebersteinii leaves   cell death   copper nanoparticles   methamphetamine   PC12  

摘要： Recently, scientist have used metallic nanoparticles for synthesizing many new drugs in the field of neurology. One of the metals used in the metallic nanoparticles is copper. The role of Achillea biebersteinii in increasing the physiological activities of central nervous system in Iranian traditional medicine is well known. In this study fresh leaves of A. biebersteinii were used for the biosynthesis of copper nanoparticles. We also assessed the effect of copper nanoparticles on methamphetamine-induced cell death in the PC12 cell line. The nanoparticles were analyzed by Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, field emission scanning electron microscopy, and ultraviolet-visible spectroscopy. A 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging experiment was carried out to assess the antioxidant properties of Cu(NO3)(2), A. biebersteinii, and CuNPs. The DPPH test revealed similar antioxidant activities for A. biebersteinii, CuNPs, and butylated hydroxytoluene. In the cellular and molecular part of the present study, the Trypan blue test was performed to assess cell viability. The terminal deoxynucleotidyl transferase 2 '-Deoxyuridine, 5 '-Triphosphate (dUTP) nick end labeling test clarified the DNA fragmentation and apoptosis occurrence. The Griess reaction was used to measure nitric oxide production and caspase-3 activity was evaluated by spectrophotometry. The obtained results were fed into SPSS-22 software and analyzed by one-way ANOVA, followed by Tukey's post hoc test (p <= 0.01). The results indicate that both doses of CuNPs had cell death-suppressing effects on nerve cells. In particular, both doses of CuNPs significantly (p <= 0.01) increased cell viability and NO production, and decreased cell cytotoxicity, cell death index, and caspase-3 activity near the normal. According to these results, it seems that CuNPs could be administrated as a neuroprotective supplement or drug fo

关键词： Chiari malformation   Idiopathic scoliosis   Motor evoked potentials   Scoliosis   Somatosensory evoked potentials   Syringomyelia  

摘要： Objectives: To analyze the somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in neurologically asymptomatic Chiari malformation-associated scoliosis (CMS) patients with and without syringomyelia as compared with those in idiopathic scoliosis (IS) ones, and to identify whether the deformities have impacts on the neurophysiological monitoring. Patients and methods: This study included neurologically asymptomatic CMS patients undergoing posterior correction surgery between January 2010 and January 2016. IS patients were involved as control group and a subgroup of age- and height-matched IS patients were selected. The age, standing height and Cobb angles of main curve were measured. The SEPs latency and amplitude, MEPs amplitude, and the rate of abnormal SEPs pathologic change were compared between CMS and IS patients using independent-sample t-test and Chi-square test. Results: Sixty CMS patients and 210 IS patients were included. There was no difference between CMS patients and IS or matched IS patients in SEPs latency and amplitude, MEPs amplitude or rate of abnormal SEPs (p > 0.05). Forty-eight CMS patients concurrent with syringomyelia were associated with higher Cobb angle of main curve and lower SEPs amplitude than those without syringomyelia (p < 0.05). No significant difference was found between CMS patients with and without syringomyelia in age, height, SEPs latency, MEPs amplitude or rate of abnormal SEPs (p > 0.05). Conclusion: Neurologically asymptomatic CMS patients showed similar absolute values of neurophysiological monitoring with IS patients. The syringomyelia in CMS indicated more severe curvature and lower SEPs amplitude even after posterior fossa decompression.

关键词： CHCHD2   CHCHD10   neurological disorders   iPSC   animal models  

摘要： CHCHD2 mutations have been identified in various neurological diseases such as Parkinson's disease (PD), frontotemporal dementia (FTD), and Alzheimer's disease (AD). It is also the first mitochondrial gene whose mutations lead to PD. CHCHD10 is a homolog of CHCHD2;similar to CHCHD2, various mutations of CHCHD10 have been identified in a broad spectrum of neurological disorders, including FTD and AD, with a high frequency of CHCHD10 mutations found in motor neuron diseases. Functionally, CHCHD2 and CHCHD10 have been demonstrated to interact with each other in mitochondria. Recent studies link the biological functions of CHCHD2 to the MICOS complex (mitochondrial inner membrane organizing system). Multiple experimental models suggest that CHCHD2 maintains mitochondrial cristae and disease-associated CHCHD2 mutations function in a loss-of-function manner. However, both CHCHD2 and CHCHD10 knockout mouse models appear phenotypically normal, with no obvious mitochondrial defects. Strategies to maintain or enhance mitochondria cristae could provide opportunities to correct the associated cellular defects in disease state and unravel potential novel targets for CHCHD2-linked neurological conditions.

关键词： Multiple sclerosis   Rare diseases   Pathophysiology   Clinical research   Therapies  

摘要： The complex biology of neurological diseases calls for collaborative efforts that may increase the success rate of clinical research. Models have been proposed, but concrete actions remain insufficient. Based on recent considerations from basic science, from science of patient input and from an analysis of scientific resources in Italy, we here explain why our country may represent an appropriate environment for such actions. Furthermore, we sketch operational framework and business model to be applied in order to accelerate, in parallel, the development of therapies in common and rare diseases.

关键词： CXCL13   chemokine   diagnostic marker   neuroborreliosis   neurosyphilis   inflammation   cerebrospinal fluid  

摘要： Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.

关键词： Antiepileptics   Drug-related problem   Generic substitution   Neurology   Parkinson's disease   Pharmacotherapy   Systematic review  

摘要： Background Generic drug exchange is common practice in most healthcare systems. While generics certainly contribute to economic savings, the altered drug formulation might be associated with potential therapeutic problems. Given the narrow therapeutic windows in neurologic indications, any detrimental effect on the therapy can lead to significant consequences. Aim of the review This review aims to investigate potential problems related to a switch from brand-name to generic or from generic to generic drug products in patients with neurologic diseases. Method The review was conducted following the PICO framework and the PRISMA guidelines. MEDLINE and Scopus databases were searched for articles published in English and German language between January 1, 1995 and October 17, 2018. Studies included in this review were randomized controlled studies, reviews, systematic reviews, overviews, cohort studies and case-control studies. Studies excluded were letters, comments, authors view, congress or seminar papers and studies with a focus on economic impact or costs. Results were synthesized qualitatively. The primary outcomes were pharmacokinetic parameters such as the area under the curve (AUC), the peak serum concentration (c(max)) or the time at which c(max) is observed (t(max)). Results The search identified 67 studies with a great variety of endpoints and study designs. The leading indication was epilepsy. Two small RCTs were found on lamotrigine switch. Analysis of the other studies found no significant differences in pharmacokinetic parameters when switching to generic drugs. A more heterogeneous picture was revealed regarding hospitalizations, breakthrough seizures, failure of therapy, adherence and patient concerns. Conclusion While most reports were of poor quality, lamotrigine was the drug with the best available data. Summarizing the results of the available studies, pharmacokinetic parameters of antiepileptic drugs show low deviation. In contrast, data on clinic

关键词： Total anterior circulation infarct   Risk score   Antiplatelet   Middle cerebral artery  

摘要： Objectives: Specific factors and its predictive parameters for neurological deterioration in total anterior circulation infarct (TACI) were not known. Our objective was to determine the risk factors and risk scores for neurological deterioration in TACI. The secondary objective was to determine the effect of antiplatelet therapy in TACI. Patients and Methods: This was a single-center cohort study. 46 patients with TACI were enrolled and followed up for 30 days, discharged, or death;whichever earlier. The National Institutes of Health Stroke Scale (NIHSS) was performed daily by investigators who are NIHSS certified and radiological findings were confirmed by a certified radiologist. Neurological deterioration was defined by a drop in NIHSS by 2 points or Glasgow Coma Scale (GCS) by 1 point. Clinical, laboratory and radiological variables were evaluated. Significant predictive variables were given a score based on its co-efficient values in multivariate analysis. Results: Lower Alberta stroke program early CT score (ASPECTS) and higher numbers of early computed tomography (CT) sign of middle cerebral artery (MCA) infarct were significant risk factor for neurological deterioration with p < 0.001 (OR: 3.41, 95% CI 1.78-6.51) and p < 0.001 (OR 18.19, 95% CI 3.82-86.55) respectively. A score of 1 assigned for 3 early CT signs of MCA infarct, 2 for 4 early CT signs of MCA infarct, and 1 for ASPECTS < 6. Receiver operating characteristic (ROC) showed a total score of 2 predicted neurological deterioration in TACI (Area under the curve 0.953, with sensitivity and specificity of 78.9% and 93% respectively). Conclusion: A simple 2 variables risk score formula was significant in predicting neurological deterioration. Antiplatelet may be recommended for TACI, further study is required.

摘要： EEG background reactivity and EEG background continuity (EEG parameters that are indicative for a favourable outcome) were associated with a more favourable MRI grading. The results of the correlation between EEG and MRI were likely influenced by pseudo normalization of the EEG.[[3], [11]] The exact additional prognostic value of MRI in patients with EEG remains to be established. [Extracted from the article]

关键词： Cerebellum   Ataxias   Therapies   RNA   DNA  

摘要： Cerebellar ataxias (CAs) represent a heterogeneous group of sporadic or inherited disorders. The clinical spectrum of CAs is continuously expanding. Our understanding of the mechanisms leading to the clinical deficits has improved over these last decades, in particular thanks to progress in genetics, neuroimaging and the advent of relevant animal models allowing the identification of the pathophysiological pathways leading to CAs. The rationale behind treatments is now established for most of the CAs encountered during daily practice worldwide. In this update, we will discuss the symptomatic, physical and occupational therapies now being trialled along with individualized exercises, and present key emerging issues on immune-mediated cerebellar ataxias, hereditary cerebellar ataxias. Finally, we will discuss novel therapeutic approaches, including cerebellar non-invasive stimulation and treatments acting on RNA/proteins. So far, no state-of-the art randomized placebo-controlled clinical trial has shown a convincing clinically relevant efficacy of any drug, with the exception of 4-aminopyridine for the symptomatic treatment of episodic ataxia type 2 and downbeat nystagmus (placebo-controlled trials).