摘要： Background: A number of awake patients undergoing carotid endarterectomy (CEA) present from test clamp neurological deficits (NDs) during the procedure. Current guidelines advocate tighter Doppler ultrasound (DUS) surveillance in these patients because of probable higher likelihood of hemodynamic stroke (class 1 grade C), although evidence is lacking regarding benefit. The aim for the study is the assumption that patients who present ND have a higher risk of developing a complete stroke if the ipsilateral carotid artery becomes occluded, and for this reason, surveillance over restenosis of endarterectomy in this group is justifiable;hence, the authors would like to contribute to this matter presenting their experience on restenosis in this specific group of patients. Methods: Data were prospectively collected between 2009 and 2018 for patients of a university tertiary referral center who underwent CEA under regional anesthesia and developed alterations in the neurologic monitoring during internal carotid artery (ICA) test clamping. Control patients were consecutively selected as the next patient submitted to the same procedure but who did not develop neurologic alterations. Patients who did not present to the first postoperative evaluation were excluded (4-6 weeks). Primary outcome was any restenosis (>30%;>50%;>70%) detected by DUS evaluations between 16 and 30 months of follow-up. Clinical adverse events such as stroke, myocardial infarction, acute heart failure, and all-cause death were assessed 30 days after the procedure and in the subsequent long-term surveillance period. A multivariate analysis of factors with significant associations to restenosis identified in a univariate analysis was performed by binary logistic regression. Kaplan-Meier analysis and life tables were used to evaluate time-dependent variables. Results: Ninety patients with ND and 94 controls were included. Those with ND had a higher prevalence of obesity, mean age, and scores of American So

关键词： Galactosemia   Development   Magnetic resonance imaging   Neurological complications  

摘要： Background- Despite implementation of a controlled diet, children with classical galactosemia (CG) may develop a variety of developmental and cognitive problems. In this study, we examined the early developmental status of, as well as the neurological and neuroradiological findings for, children with CG. Methods: We retrospectively evaluated 46 galactosemia patients who were followed between 2003 and 2017. We included those who exhibited CG and ***188arg homozygous mutation without concomitant disease and who had undergone detailed neurological examination, brain magnetic resonance imaging (MRI), and Denver II developmental testing. Results: The mean ages at the time of the most recent neurological examination and Denver II testing were 48.5 +/- 28.5 months and 34.4 +/- 18.2 months, respectively. Developmental delay was defined as develop. mental age >= 20% lower than chronological age. The results were normal in 25 patients and delayed >= 20% in least in one domain, primarily in language development, in 21 patients. Brain MRI was abnormal in 22 patients. Conclusions: This analysis of the youngest children with the same genetic mutation reported thus far showed that, despite treatment, developmental delays and abnormalities on brain MRI may begin at an early age.

关键词： Disease genetics   Genetics research  

摘要： Sphingolipidoses are monogenic lipid storage diseases caused by variants in enzymes of lipid synthesis and metabolism. We describe an autosomal recessive complex neurological disorder affecting consanguineous kindred. All four affected individuals, born at term following normal pregnancies, had mild to severe intellectual disability, spastic quadriplegia, scoliosis and epilepsy in most, with no dysmorphic features. Brain MRI findings were suggestive of leukodystrophy, with abnormal hyperintense signal in the periventricular perioccipital region and thinning of the body of corpus callosum. Notably, all affected individuals were asymptomatic at early infancy and developed normally until the age of 8-18 months, when deterioration ensued. Homozygosity mapping identified a single 8.7 Mb disease-associated locus on chromosome 1q41-1q42.13 between rs1511695 and rs537250 (two-point LOD score 2.1). Whole exome sequencing, validated through Sanger sequencing, identified within this locus a single disease-associated homozygous variant in DEGS1, encoding C4-dihydroceramide desaturase, an enzyme of the ceramide synthesis pathway. The missense variant, segregating within the family as expected for recessive heredity, affects an evolutionary-conserved amino acid of all isoforms of DEGS1 (c.656A>G, c.764A>G;p.(N219S), p.(N255S)) and was not found in a homozygous state in ExAC and gnomAD databases or in 300 ethnically matched individuals. Lipidomcs analysis of whole blood of affected individuals demonstrated augmented levels of dihydroceramides, dihydrosphingosine, dihydrosphingosine-1-phosphate and dihydrosphingomyelins with reduced levels of ceramide, sphingosine, sphingosine- 1 -phosphate and monohexosylceramides, as expected in malfunction of C4-dihydroceramide desaturase. Thus, we describe a sphingolipidosis causing a severe regressive neurological disease.

关键词： Paraneoplastic   Autoimmune   Encephalitis   Panel   Utilization   Cost  

摘要： Objectives: The field of paraneoplastic neurological syndromes PNS has grown exponentially with the increased identification of associated antibodies. Testing for these antibodies is commonly done in "panels" to increase sensitivity, and these panels have become a routine test on CSF samples obtained for a variety of clinical indications. Excessive testing has raised concerns about the correct utilization of these panels. Our study investigates the appropriateness of use of paraneoplastic panel in an academic, tertiary-care medical center. Patients and Methods: We retrospectively reviewed charts of all patients who had autoimmune paraneoplastic panel testing in one year period. We collected date on demographics, clinical presentations and ancillary testings on all reviewed charts. Then, we devised an algorithm based on available data to define cases where testing had been unnecessary or likely unnecessary. Results: We collected 60 cases that had undergone autoimmune paraneoplastic testing serum and/or CSF. Testing was unnecessary in 10 cases (16%), in which presentations had a definitive confirmatory tests. Testing was unlikely necessary in 11 cases (18%), in which all ancillary testing was normal in 6 cases, and presentation was not compatible with any known syndrome in 5 cases. Collectively, paraneoplastic panel testing was of extremely low yield on more than one third of the cases where where w testing was done. Conclusion Our results adds to the growing concerns about the utilization of paraneoplastic panels, and the urgent need for enhanced screening and establishing a framework that can guide neurologists on when testing can have a sufficient yield to warrant it. Such framework should be built using diagnostic algorithms based on risk, clinical manifestations, characterization of autoantibodies and their associations.

关键词： Neurogenic stunned myocardium   Stress cardiomyopathy   Takotsubo cardiomyopathy   Subarachnoid hemorrhage   Severe traumatic brain injury  

摘要： Purpose of Review Neurogenic stunned myocardium (NSM) is a poorly recognized cardiac manifestation of neurological illness. This review addresses the contemporary understanding of NSM pathophysiology, epidemiology, diagnosis, and clinical management. Recent Findings While the precise pathophysiology and diagnosis remain unclear, NSM is phenotypically atypical stress cardiomyopathy that can be partially attributed to excess catecholaminergic toxicity. NSM is a diagnosis of exclusion where electrocardiography, echocardiography, and cardiac biomarkers are frequently abnormal. Clinical expertise is crucial to evaluate and differentiate NSM from acute coronary syndrome and in the evaluation of potential cardiac transplantation donors after unsalvageable severe neurological injury. Neurogenic stunned myocardium is a relatively common and clinically impactful condition. More research is needed, particularly to refine clinical prognostication of NSM and rule out intrinsic cardiac injury in order to optimize donor candidacy in the event of brain death.

关键词： Propionate   Pentylenetetrazol   Seizure   Mitochondrial disruption   Neurological deficits  

摘要： The present research was designed to evaluate the protective effects and underlying mechanisms of propionate, a bioactive food additive, on mitochondrial disruption, neuron necrosis and neurological deficits after epilepsy seizures. Epilepsy seizures was induced by repetitive injections of pentylenetetrazol at a dose of 37 mg per kg. Propionate (37.5, 50 and 75 mg/kg) as well as sodium valproate (300 mg/kg) were administrated intragastrically (i.g.) 1 h before each PTZ injection and continued for 40 days. The influence of propionate was assessed by many biochemical assays and neurobehavioral experiments. The results of gas chromatography (GC) analysis indicated that increased concentration of propionate can be explored in hippocampus area of propionate + PTZ treated animals. Propionate decreased epilepsy seizure intensity, increased latency of seizures. Meanwhile, propionate treatment reversed the structure disruption of the mitochondria, improved ATP level and lessened 8-OHdG level in the brains of animals with seizures. In addition, we find propionate pre-treated can increase activities of the antioxidant enzymes (CAT, SOD, as well as GSH-Px) in mitochondria. Additionally, propionate reduced neuronal loss in hippocampus and our results suggest that HIF-1 alpha/ERK pathway and neuron necrosis exists potential linkage during epileptogenesis. Moreover, as a result, propionate administration can significantly improve the neurological function estimated by a battery of functional tests. In conclusion, treatment with propionate attenuates mitochondrial disruption, hippocampal apoptosis and neurological deficits in a mouse model of epilepsy seizures. Therefore, propionate, currently used as a food preservative, has a potential additional advantage of ameliorating epilepsy seizures.

关键词： Delirium   Confusional state   Neuropsychiatry   Dopamine   Homovanillic acid   Autoimmune limbic encephalitis  

摘要： Background. Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. Aim. To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. Methods. A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. Results. 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. Conclusions. In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium. (C) 2019 IMSS. Published by Elsevier Inc.

关键词： cardiovascular disease   developmental origins of health and disease (DOHaD)   developmental programming   hypertension   melatonin   neurological disease   lactation   oxidative stress   pregnancy  

摘要： Cardiovascular and neurological diseases can originate in early life. Melatonin, a biologically active substance, acts as a pleiotropic hormone essential for pregnancy and fetal development. Maternal melatonin can easily pass the placenta and provide photoperiodic signals to the fetus. Though melatonin uses in pregnant or lactating women have not yet been recommended, there is a growing body of evidence from animal studies in support of melatonin as a reprogramming strategy to prevent the developmental programming of cardiovascular and neurological diseases. Here, we review several key themes in melatonin use in pregnancy and lactation within offspring health and disease. We have particularly focused on the following areas: the pathophysiological roles of melatonin in pregnancy, lactation, and fetal development;clinical uses of melatonin in fetal and neonatal diseases;experimental evidence supporting melatonin as a reprogramming therapy to prevent cardiovascular and neurological diseases;and reprogramming mechanisms of melatonin within developmental programming. The targeting of melatonin uses in pregnancy and lactation will be valuable in the prevention of various adult chronic diseases in later life, and especially cardiovascular and neurological diseases.

关键词： Programmed death 1   Programmed death ligand 1   Surgical brain injury   Microglia   Astrocyte  

摘要： Neuroinflammation and brain edema are major complications in the pathophysiology of surgical brain injury (SBI). Programmed death-ligand 1 (PD-L1), an immune inhibitory receptor ligand, has been increasingly investigated for inhibition of T cell-mediated immunity and braking inflammatory response. However, the negative immunomodulatory capacity of PD-L1 and their possible mechanism in SBI is not yet clear. This study aimed to evaluate the expression and the role of PD-L1 in a mouse model of SBI induced inflammation and to further study the potential therapeutic effects of PD-L1 on SBI. Here we showed that PD-L1 expression was markedly elevated in the surrounding peri-resection brain tissue post-SBI in vivo. PD-L1 was up-regulated through ERK signal pathway in LPS-treated BV-2 cells in vitro. Furthermore, blockade of the PD-L1 checkpoint using PD-L1 antibody significantly enhanced brain edema, exacerbated apoptosis and increased neurodeficits post-SBI. Moreover, activated PD-1/PD-L1 with PD-L1 protein significantly attenuated the inflammation responses and brain edema post-SBI. These results suggest that enhanced expression of PD-L1 post-SBI exerts self-protection from inflammation and promotes neurological repair. PD-L1 signal may have therapeutic potential for neurodegenerative disorders.