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

Reversible cerebral vasoconstriction syndrome induced by adrenaline

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute severe thunderclap headaches and evidence of multifocal, segmental, reversible vasoconstrictions of the cerebral arteries. Several precipitating factors have been identified and reported, including the use of recreational substances or sympathomimetic drugs and the postpartum state. Case description: Here we present the case of a woman who developed RCVS after the administration of adrenaline (epinephrine) in the setting of an anaphylactic reaction during antibiotic allergy testing. Discussion: To our knowledge, this is the first reported case of RCVS following the administration of exogenous adrenaline. This case contributes to the understanding of the physiopathological mechanisms underlying reversible cerebral vasoconstrictio

Neutrophils self-limit swarming to contain bacterial growth in vivo

Neutrophils communicate with each other to form swarms in infected organs. Coordination of this population response is critical for the elimination of bacteria and fungi. Using transgenic mice, we found that neutrophils have evolved an intrinsic mechanism to self-limit swarming and avoid uncontrolled aggregation during inflammation. G protein–coupled receptor (GPCR) desensitization acts as a negative feedback control to stop migration of neutrophils when they sense high concentrations of self-secreted attractants that initially amplify swarming. Interference with this process allows neutrophils to scan larger tissue areas for microbes. Unexpectedly, this does not benefit bacterial clearance as containment of proliferating bacteria by neutrophil clusters becomes impeded. Our data reveal how autosignaling stops self-organized swarming behavior and how the finely tuned balance of neutrophil chemotaxis and arrest counteracts bacterial escape

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

Experiencia clínica del tratamiento con onabotulinumtoxin A en pacientes con migraña refractaria

To analyse our experience in the treatment of refractory chronic migraine, episodic frequent refractory migraine (>= 10 days/month), with onabotulinumtoxin A (OnabotA). PATIENTS AND METHODS. Retrospective analysis of patients with refractory migraine who underwent, at least two sessions of OnabotA pericranial injections following the PREEMPT protocol between 2008 and 2012. The efficacy of OnabotA was evaluated comparing the basal situation with 12-16 weeks after the second session. We analysed the subjective improvement of the patients, number of days with headache, preventive and abortive drugs consumption, and adverse effects. RESULTS. Forty-one patients (37 women, 4 male) were identified. 65.8% patients experienced subjective improvement after OnabotA treatment. 36.58% responded (reduction of > 50% in headache days). Differences between days with headache before the first session (24.5 +/- 7.3), and 12-16 weeks after the second session (17.4 +/- 11.6), as well as the differences between the number of abortive drugs taken before the first session (26.8 +/- 23.1) and 12-16 weeks after the second session (16.7 +/- 19.3), were statistically significant (p < 0.001). Subgroups analysis showed that all differences were significant, except for the reduction of the number of days with headache in patients with episodic frequent refractory migraine. CONCLUSION. Our work shows that treatment with OnabotA is safe and useful in patients with episodic and chronic refractory migraine, including those patients with medication overuse headache

Patient-Tailored Connectomics Visualization for the Assessment of White Matter Atrophy in Traumatic Brain Injury

Available approaches to the investigation of traumatic brain injury (TBI) are frequently hampered, to some extent, by the unsatisfactory abilities of existing methodologies to efficiently define and represent affected structural connectivity and functional mechanisms underlying TBI-related pathology. In this paper, we describe a patient-tailored framework which allows mapping and characterization of TBI-related structural damage to the brain via multimodal neuroimaging and personalized connectomics. Specifically, we introduce a graphically driven approach for the assessment of trauma-related atrophy of white matter connections between cortical structures, with relevance to the quantification of TBI chronic case evolution. This approach allows one to inform the formulation of graphical neurophysiological and neuropsychological TBI profiles based on the particular structural deficits of the affected patient. In addition, it allows one to relate the findings supplied by our workflow to the existing body of research that focuses on the functional roles of the cortical structures being targeted. A graphical means for representing patient TBI status is relevant to the emerging field of personalized medicine and to the investigation of neural atrophy

Huntington's disease-specific mis-splicing unveils key effector genes and altered splicing factors

Correction of mis-splicing events is a growing therapeutic approach for neurological diseases such as spinal muscular atrophy or neuronal ceroid lipofuscinosis 7, which are caused by splicing-affecting mutations. Mis-spliced effector genes that do not harbour mutations are also good candidate therapeutic targets in diseases with more complex aetiologies such as cancer, autism, muscular dystrophies or neurodegenerative diseases. Next-generation RNA sequencing (RNA-seq) has boosted investigation of global mis-splicing in diseased tissue to identify such key pathogenic mis-spliced genes. Nevertheless, while analysis of tumour or dystrophic muscle biopsies can be informative on early stage pathogenic mis-splicing, for neurodegenerative diseases, these analyses are intrinsically hampered by neuronal loss and neuroinflammation in post-mortem brains. To infer splicing alterations relevant to Huntington's disease pathogenesis, here we performed intersect-RNA-seq analyses of human post-mortem striatal tissue and of an early symptomatic mouse model in which neuronal loss and gliosis are not yet present. Together with a human/mouse parallel motif scan analysis, this approach allowed us to identify the shared mis-splicing signature triggered by the Huntington's disease-causing mutation in both species and to infer upstream deregulated splicing factors. Moreover, we identified a plethora of downstream neurodegeneration-linked mis-spliced effector genes that-together with the deregulated splicing factors-become new possible therapeutic targets. In summary, here we report pathogenic global mis-splicing in Huntington's disease striatum captured by our new intersect-RNA-seq approach that can be readily applied to other neurodegenerative diseases for which bona fide animal models are available.Extremadura Research Centre for Advanced Technologies (CETA-CIEMAT), funded by the European Regional Development Fund (ERDF). CETA-CIEMAT belongs to CIEMAT and the Government of Spai

RM en el diagnóstico y control evolutivo de la degeneración combinada subaguda. A propósito de un caso

A deficit of vitamin B12, generally resulting from pernicious anaemia, can give rise to disorders of the spinal cord, brain, optic and peripheral nerves. The principal neurological syndrome is subacute combined degeneration of the spinal cord (SCD), which can cause progressive motor and/or sensitive alterations, instability and incontinency, due to the demyelination of the posterior horn of the spinal cord. The identification by magnetic resonance (MR) of signal hyperintensity in T2 weighted sequences at the level of the posterior horns of the spinal and/or cervical cord can be of great use in diagnosising the patient with SCD, above all when the symptoms are mild or nonspecific, and the patient does not have haematological or gastrointestinal alterations. Besides, the evolution of the altered signal of the posterior horns in MR can be of use in evaluating the efficacy of treatment, since their normalization is related to clinical improvemen

Spitzer reveals what's behind Orion's Bar

We present Spitzer Space Telescope observations of 11 regions SE of the Bright Bar in the Orion Nebula, along a radial from the exciting star theta1OriC, extending from 2.6 to 12.1'. Our Cycle 5 programme obtained deep spectra with matching IRS short-high (SH) and long-high (LH) aperture grid patterns. Most previous IR missions observed only the inner few arcmin. Orion is the benchmark for studies of the ISM particularly for elemental abundances. Spitzer observations provide a unique perspective on the Ne and S abundances by virtue of observing the dominant ionization states of Ne (Ne+, Ne++) and S (S++, S3+) in Orion and H II regions in general. The Ne/H abundance ratio is especially well determined, with a value of (1.01+/-0.08)E-4. We obtained corresponding new ground-based spectra at CTIO. These optical data are used to estimate the electron temperature, electron density, optical extinction, and the S+/S++ ratio at each of our Spitzer positions. That permits an adjustment for the total gas-phase S abundance because no S+ line is observed by Spitzer. The gas-phase S/H abundance ratio is (7.68+/-0.30)E-6. The Ne/S abundance ratio may be determined even when the weaker hydrogen line, H(7-6) here, is not measured. The mean value, adjusted for the optical S+/S++ ratio, is Ne/S = 13.0+/-0.6. We derive the electron density versus distance from theta1OriC for [S III] and [S II]. Both distributions are for the most part decreasing with increasing distance. A dramatic find is the presence of high-ionization Ne++ all the way to the outer optical boundary ~12' from theta1OriC. This IR result is robust, whereas the optical evidence from observations of high-ionization species (e.g. O++) at the outer optical boundary suffers uncertainty because of scattering of emission from the much brighter inner Huygens Region.Comment: 60 pages, 16 figures, 10 tables. MNRAS accepte

Plasmon oscillations in ellipsoid nanoparticles: beyond dipole approximation

The plasmon oscillations of a metallic triaxial ellipsoid nanoparticle have been studied within the framework of the quasistatic approximation. A general method has been proposed for finding the analytical expressions describing the potential and frequencies of the plasmon oscillations of an arbitrary multipolarity order. The analytical expressions have been derived for an electric potential and plasmon oscillation frequencies of the first 24 modes. Other higher orders plasmon modes are investigated numerically.Comment: 33 pages, 12 figure