Tratamiento médico de la estenosis arterial intracraneal. ¿Es el mismo en prevención primaria que en secundaria?

In this study we review the risk factors associated with the formation and progression of an atheroma plaque, the mechanism involved in cerebral ischemia secondary to intracranial atheromatosis and possible medical treatment in primary and secondary prevention. DEVELOPMENT: Medical treatment of intracranial stenoses (ICS) is aimed at stopping the progression of the atheroma plaque and at preventing recurrences in the case of symptomatic stenoses. It is based on the control of vascular risk factors, the use of statins and antithrombotic therapy (antiplatelet or anticoagulation drugs). Although antiplatelet agents have not proved to be beneficial in the primary prevention of stroke, they are recommended in patients with ICS in order to lower the risk of heart attack associated with this pathology. The use of antiplatelet drugs in the secondary prevention of ischemic stroke secondary to an ICS is based on clinical trials which have shown that antiaggregation prevents non-cardioembolic strokes. Nevertheless, several retrospective studies have observed that oral anticoagulation is better than antiaggregation with aspirin. Two prospective clinical trials are currently being conducted which will, in the next few years, help to determine what the first choice medical treatment is for this group of patients. CONCLUSIONS: Medical treatment of ICS patients must include the control of vascular risk factors and the use of statins. New studies are needed to be able to establish the first choice antithrombotic drug in secondary prevention

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Cefalea en urgencias

Headache is among the most frequent neurological symptoms in the Emergency department. Although most of the patients suffer from primary headaches (migraine), an acute headache might be the only symptom of a serious disease, such as subarachnoid haemorrhage. The physician’s task is to make the diagnosis, carry out an appropriate selection of the patients who require further diagnostic evaluation and relieve the pain. An accurate history will identify most of the patients with secondary headaches. Clinicians should suspect secondary causes in sudden onset headache, headache in patients aged over 50 years, and also in those patients with abnormalities on neurological examination

Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice

Glycogen, the repository of glucose in many cell types, contains small amounts of covalent phosphate, of uncertain function and poorly understood metabolism. Loss-of-function mutations in the laforin gene cause the fatal neurodegenerative disorder, Lafora disease, characterized by increased glycogen phosphorylation and the formation of abnormal deposits of glycogen-like material called Lafora bodies. It is generally accepted that the phosphate is removed by the laforin phosphatase. To study the dynamics of skeletal muscle glycogen phosphorylation in vivo under physiological conditions, mice were subjected to glycogen-depleting exercise and then monitored while they resynthesized glycogen. Depletion of glycogen by exercise was associated with a substantial reduction in total glycogen phosphate and the newly resynthesized glycogen was less branched and less phosphorylated. Branching returned to normal on a time frame of days, whereas phosphorylation remained suppressed over a longer period of time. We observed no change in markers of autophagy. Exercise of 3-month-old laforin knock-out mice caused a similar depletion of glycogen but no loss of glycogen phosphate. Furthermore, remodeling of glycogen to restore the basal branching pattern was delayed in the knock-out animals. From these results, we infer that 1) laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen, 2) excess glycogen phosphorylation in the absence of laforin delays the normal remodeling of the branching structure, and 3) the accumulation of glycogen phosphate is a relatively slow process involving multiple cycles of glycogen synthesis-degradation, consistent with the slow onset of the symptoms of Lafora disease

Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice

Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3-/- . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA

Estimation of the Economic Burden and Labor Impact of Migraine in Spain: Results from the Spanish Atlas of Migraine Survey 2018

P170 Objectives: To estimate the average annual cost per patient and theimpact on work t of migraine in Spain. Material and Method: This is a prospective, online, anonymous, cross-sectional survey, conducted between June and September2017, promoted by the Spanish Association of Patients with Headache(AEPAC) within the framework of the Spanish Atlas of Migraine2018. People who completed the survey answered questions in relationto their migraine. A distinction was made between chronic migraine(CM) and episodic migraine (EM), considering the monthlyheadache days declared by patients. The economic burden of migrainewas evaluated: direct health costs (including visits to specialists, medical tests, emergency visits, hospital admissions andmedication), indirect costs (lost labor productivity), and those assumedby the migraineur. The labor consequences of migraine overthe last year were analyzed. Chi-square and Mann- Whitney testswere used as contrast tests. Ethics Approval: A central ethics reviewboard approved the study design. Results: 1, 281 people with migraine participated in the survey, 34.2%with CM, 88.2% women, with an average age of 37.3 (SD 11.5). Thedirect health costs for the last year were estimated at €3, 847.29 forCM and €964.19 for EM (p<0, 001). The costs assumed by the patientin the last year were €1, 609.89 for CM and €878.04 for EM (p<0.001).The indirect cost was estimated at €7, 464.83 for CM and €3, 199.15for EM (p <0.001). The total average cost per patient/year rised to€12, 922.01 for CM and €5, 041.41 for EM (p<0.001). Regarding the jobstatus: 62.2% with EM and 49.0% with CM were working, 2.6% withEM and 9.1% with CM were on sick leave and 12.2% with EM and16.8% with CM were unemployed (p <0.05). In the last year, becauseof migraine, 17.8% of patients with EM and 27.2% with CM (p<0.01)requested days of leave or leave of absence, and reduced their workinghours 8.5% with EM and 11.1% CM (p=0.270). Labor efficiencywas reduced in 61.1% of patients with EM and 65.7% with CM(p=0.257). Conclusion: Migraine represents an important economic burden inSpain, particularly in patients with CM. Migraine causes importantproductivity losses resulting from absenteeism, presentism, decreasingthe working hours and the probabilities to keep working, and itsimpact is significantly greater in CM

Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise

As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n = 9) or without (BR; n = 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α), and myostatin, were analyzed in samples from m. vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1α and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle

Preferential binding of a stable G3BP ribonucleoprotein complex to intron-retaining transcripts in mouse brain and modulation of their expression in the cerebellum.

Neuronal granules play an important role in the localization and transport of translationally silenced messenger ribonucleoproteins (mRNPs) in neurons. Among the factors associated with these granules, the RNA-binding protein G3BP1 (stress-granules assembly factor) is involved in neuronal plasticity and is induced in Alzheimer's disease. We immunopurified a stable complex containing G3BP1 from mouse brain and performed High-Throughput Sequencing and CrossLinking Immunoprecipitation (HITS-CLIP) to identify the associated RNAs. The G3BP-complex contained the deubiquitinating protease USP10, CtBP1 and the RNA binding proteins Caprin-1, G3BP2a and SFPQ (Splicing Factor Proline and Glutamine rich, or PSF). The G3BP-complex binds preferentially to transcripts that retain introns, and to non-coding sequences like 3'UTR and long non-coding RNAs. Specific transcripts with retained introns appear to be enriched in the cerebellum compared to the rest of the brain and G3BP1 depletion decreased this intron retention in the cerebellum of G3BP1 knockout mice. Among the enriched transcripts, we found an overrepresentation of genes involved in synaptic transmission, especially glutamate-related neuronal transmission. Notably, G3BP1 seems to repress the expression of the mature Grm5 (metabotropic glutamate receptor 5) transcript, by promoting the retention of an intron in the immature transcript in the cerebellum. Our results suggest that G3BP is involved in a new functional mechanism to regulate non-coding RNAs including intron-retaining transcripts, and thus have broad implications for neuronal gene regulation, where intron retention is widespread. This article is protected by copyright. All rights reserved

Support Vector Machines, Multidimensional Scaling and Magnetic Resonance Imaging Reveal Structural Brain Abnormalities Associated With the Interaction Between Autism Spectrum Disorder and Sex

Despite substantial efforts, it remains difficult to identify reliable neuroanatomic biomarkers of autism spectrum disorder (ASD) based on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Studies which use standard statistical methods to approach this task have been hampered by numerous challenges, many of which are innate to the mathematical formulation and assumptions of general linear models (GLM). Although the potential of alternative approaches such as machine learning (ML) to identify robust neuroanatomic correlates of psychiatric disease has long been acknowledged, few studies have attempted to evaluate the abilities of ML to identify structural brain abnormalities associated with ASD. Here we use a sample of 110 ASD patients and 83 typically developing (TD) volunteers (95 females) to assess the suitability of support vector machines (SVMs, a robust type of ML) as an alternative to standard statistical inference for identifying structural brain features which can reliably distinguish ASD patients from TD subjects of either sex, thereby facilitating the study of the interaction between ASD diagnosis and sex. We find that SVMs can perform these tasks with high accuracy and that the neuroanatomic correlates of ASD identified using SVMs overlap substantially with those found using conventional statistical methods. Our results confirm and establish SVMs as powerful ML tools for the study of ASD-related structural brain abnormalities. Additionally, they provide novel insights into the volumetric, morphometric, and connectomic correlates of this epidemiologically significant disorder