Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave Dreams Study (Brain Venous Drainage Exploited Against Multiple Sclerosis): study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins.Study design and methodsThis is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment. DISCUSSION: The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.Trial registrationClinicaltrials.gov NCT01371760

On the magnetosphere-ionosphere coupling during the May 2021 geomagnetic storm

On 12 May 2021 the interplanetary doppelganger of the 9 May 2021 coronal mass ejection impacted the Earth's magnetosphere, giving rise to a strong geomagnetic storm. This paper discusses the evolution of the various events linking the solar activity to the Earth's ionosphere with special focus on the effects observed in the circumterrestrial environment. We investigate the propagation of the interplanetary coronal mass ejection and its interaction with the magnetosphere-ionosphere system in terms of both magnetospheric current systems and particle redistribution, by jointly analyzing data from interplanetary, magnetospheric, and low Earth orbiting satellites. The principal magnetospheric current system activated during the different phases of the geomagnetic storm was correctly identified through the direct comparison between geosynchronous orbit observations and model predictions. From the particle point of view, we have found that the primary impact of the storm development is a net and rapid loss of relativistic electrons from the entire outer radiation belt. Our analysis shows no evidence for any short-term recovery to pre-storm levels during the days following the main phase. Storm effects also included a small Forbush decrease driven by the interplay between the interplanetary shock and subsequent magnetic cloud arrival

Time dependence of the e^- flux measured by PAMELA during the July 2006 - December 2009 solar minimum

Precision measurements of the electron component in the cosmic radiation provide important information about the origin and propagation of cosmic rays in the Galaxy not accessible from the study of the cosmic-ray nuclear components due to their differing diffusion and energy-loss processes. However, when measured near Earth, the effects of propagation and modulation of galactic cosmic rays in the heliosphere, particularly significant for energies up to at least 30 GeV, must be properly taken into account. In this paper the electron (e^-) spectra measured by PAMELA down to 70 MeV from July 2006 to December 2009 over six-months time intervals are presented. Fluxes are compared with a state-of-the-art three-dimensional model of solar modulation that reproduces the observations remarkably well.Comment: 40 pages, 18 figures, 1 tabl

Search for anisotropies in cosmic-ray positrons detected by the PAMELA experiment

The PAMELA detector was launched on board of the Russian Resurs-DK1 satellite on June 15, 2006. Data collected during the first four years have been used to search for large-scale anisotropies in the arrival directions of cosmic-ray positrons. The PAMELA experiment allows for a full sky investigation, with sensitivity to global anisotropies in any angular window of the celestial sphere. Data samples of positrons in the rigidity range 10 GV $\leq$ R $\leq$ 200 GV were analyzed. This article discusses the method and the results of the search for possible local sources through analysis of anisotropy in positron data compared to the proton background. The resulting distributions of arrival directions are found to be isotropic. Starting from the angular power spectrum, a dipole anisotropy upper limit \delta = 0.166 at 95% C.L. is determined. Additional search is carried out around the Sun. No evidence of an excess correlated with that direction was found.Comment: The value of the dipole anisotropy upper limit has been changed. The method is correct but there was a miscalculation in the relative formul

Geomagnetically trapped, albedo and solar energetic particles: trajectory analysis and flux reconstruction with PAMELA

The PAMELA satellite experiment is providing comprehensive observations of the interplanetary and magnetospheric radiation in the near-Earth environment. Thanks to its identification capabilities and the semi-polar orbit, PAMELA is able to precisely measure the energetic spectra and the angular distributions of the different cosmic-ray populations over a wide latitude region, including geomagnetically trapped and albedo particles. Its observations comprise the solar energetic particle events between solar cycles 23 and 24, and the geomagnetic cutoff variations during magnetospheric storms. PAMELA's measurements are supported by an accurate analysis of particle trajectories in the Earth's magnetosphere based on a realistic geomagnetic field modeling, which allows the classification of particle populations of different origin and the investigation of the asymptotic directions of arrival.Comment: Accepted for publication in Advances in Space Research, 2016. 21 pages, 7 figure

Measurement of boron and carbon fluxes in cosmic rays with the PAMELA experiment

The propagation of cosmic rays inside our galaxy plays a fundamental role in shaping their injection spectra into those observed at Earth. One of the best tools to investigate this issue is the ratio of fluxes for secondary and primary species. The boron-to-carbon (B/C) ratio, in particular, is a sensitive probe to investigate propagation mechanisms. This paper presents new measurements of the absolute fluxes of boron and carbon nuclei, as well as the B/C ratio, from the PAMELA space experiment. The results span the range 0.44 - 129 GeV/n in kinetic energy for data taken in the period July 2006 - March 2008

Trapped proton fluxes at low Earth orbits measured by the PAMELA experiment

We report an accurate measurement of the geomagnetically trapped proton fluxes for kinetic energy above > 70 MeV performed by the PAMELA mission at low Earth orbits (350-610 km). Data were analyzed in the frame of the adiabatic theory of charged particle motion in the geomagnetic field. Flux properties were investigated in detail, providing a full characterization of the particle radiation in the South Atlantic Anomaly region, including locations, energy spectra and pitch angle distributions. PAMELA results significantly improve the description of the Earth's radiation environment at low altitudes placing important constraints on the trapping and interaction processes, and can be used to validate current trapped particle radiation models.Comment: 22 pages, 5 figure