Prognostic value of clinical neuroimaging in the investigation of minor ischaemic stroke and transient ischaemic attack

Stroke is the largest cause of adult neurological disability in the UK and up to 40% of disabling strokes are preceded by a minor ischaemic stroke or transient ischaemic attack (TIA). As the prompt initiation of preventative therapy can reduce the risk of recurrent stroke by up to 80%, there is a need for highly organised services and optimised secondary prevention therapies. Neuroimaging is fundamental to the investigation of cerebrovascular events and, when coupled with prognostic information, can contribute to tailored secondary prevention therapy. In this thesis, I aimed to provide new insights into the role of neuroimaging in the prognostication of minor ischaemic stroke and TIA, in order to assist clinical decision making and patient counselling. Data used in this thesis have been obtained from the Oxford Vascular Study (OXVASC); an ongoing prospective, population-based incidence study of vascular disease in Oxfordshire, operational since 1st April 2002. The OXVASC population comprises around 93,000 individuals, predominately Caucasian, defined by registration with one of nine primary care practices. Multiple overlapping methods are used to identify all patients with acute vascular events. Patients consecutively recruited to OXVASC with minor ischaemic stroke or TIA, irrespective of age, were included. All imaging was performed at the John Radcliffe Hospital and was with magnetic resonance imaging (MRI)/ MR-angiogram, or computed tomography (CT)/ CT-angiogram if MRI was contraindicated. I reviewed all imaging blinded to the report of the study neuroradiologist. I report several key findings in this thesis. First, intracranial atherosclerotic stenosis (ICS) was found in 19% of patients with the highest rates at older ages (21.2% at age ≥90 years). Although symptomatic ICS conveyed an increased risk of ischaemic stroke compared to no ICS (adjusted hazard ratio [HR]= 2.1, 95% CI 1.1- 3.7), the risks of same-territory ischaemic stroke in patients with 70- 99% symptomatic ICS tended to be less than those reported in the non-stenting arms of the trials, validating the role of intensive medical management in routine clinical practice. Asymptomatic ICS did not convey additional risk of vascular events or death. Second, diffusion-weighted imaging (DWI) lesions predicted an increased risk of recurrent ischaemic stroke after minor ischaemic stroke with NIHSS 0-1 and TIA up to 10 years (HR= 3.0, 1.3- 7.1 and 2.7, 1.3- 5.5, respectively), and the strongest predictive value was in patients with a cryptogenic aetiology (HR= 4.7, 1.7- 12.9). Third, 5% of patients referred to an acute neurovascular clinic harbour an asymptomatic, incidental unruptured intracranial aneurysm. Although this is almost double the rate in the general population, the subsequent risk of aneurysm rupture was low (4.6 subarachnoid haemorrhages per 1,000 person-years) in the context of intensively managed vascular risk factors and guideline-based surveillance and intervention

A ROSAT HRI Observation of the Supernova Remnant G109.1 – 1.0

We present results of a search using ROSAT HRI data for X-ray spatial substructures in the galactic supernova remnant G109.1 – 1.0 which might indicate a connection between the remnant’s bright X-ray blob and its X-ray pulsar, 1E2259 + 586. A 0.1 – 2.4 keV HRI image, created by combining separate 28- and 22-ks pointings, reveals the presence of a few small-scale X-ray features, including a NE-SW emission ridge in the remnant’s X-ray blob. Two diffuse knots in the X-ray blob, previously suggested as being aligned with the X-ray pulsar, appear to be statistical fluctuations in the Einstein HRI data. We find no morphological evidence in the X-ray spatial substructures of G109.1 – 1.0 to support a pulsar jet origin for the X-ray blob as proposed by Gregory & Fahlman

A new method of observing weak extended x-ray sources with RHESSI

We present a new method, fan-beam modulation, for observing weak extended x-ray sources with the Reuven Ramaty High-Energy Solar Spectroscopic Imager (RHESSI). This space-based solar x-ray and gamma-ray telescope has much greater sensitivity than previous experiments in the 3-25 keV range, but is normally not well suited to detecting extended sources since their signal is not modulated by RHESSI's rotating grids. When the spacecraft is offpointed from the target source, however, the fan-beam modulation time-modulates the transmission by shadowing resulting from exploiting the finite thickness of the grids. In this paper we detail how the technique is implemented and verify its consistency with sources with clear known signals that have occurred during RHESSI offpointing: microflares and the Crab Nebula. In both cases the results are consistent with previous and complementary measurements. Preliminary work indicates that this new technique allows RHESSI to observe the integrated hard x-ray spectrum of weak extended sources on the quiet Sun.Comment: Publishe

Optical Imaging and Spectroscopy of the Galactic Supernova Remnant 3C 58 (G130.7+3.1)

We present a comprehensive imaging and spectroscopic survey of optical emission knots associated with the young Galactic supernova remnant 3C 58. Hα images show hundreds of clumpy filaments and knots arranged in a complex structure covering a nearly circular area roughly 400\u27\u27 in diameter. A quite different emission structure is seen in [O III], where the brightest features are less clumpy and largely confined to the remnant\u27s northwest quadrant. Measured radial velocities of over 450 knots reveal two distinct kinematic populations; one with average and peak expansion velocities of 770 and 1100 km s−1, respectively, forming a thick shell, and the other showing |v| ≤ 250 km s−1. High-velocity knots (|v| ≥ 500 km s−1) exhibit a strong bipolar expansion pattern with redshifted and blueshifted knots located in northeastern and southwestern regions, respectively. These knots also show strong [N II]/Hα line emission ratios, suggesting enhanced N/H. In contrast, the slower expanding knot population shows much lower [N II]/Hα line ratios and likely represents circumstellar mass loss material from the 3C 58 progenitor. Proper-motion estimates using images spanning a 28 yr time interval suggest positional shifts of between 0.5\u27\u27 and 2.0\u27\u27, implying proper motions of 0.02\u27\u27-0.07\u27\u27 yr−1. These values agree with previous estimates but are much less than the ≈0.2\u27\u27 yr−1 expected if 3C 58 were associated with historic guest star of 1181 CE

Max '91: Flare research at the next solar maximum

To address the central scientific questions surrounding solar flares, coordinated observations of electromagnetic radiation and energetic particles must be made from spacecraft, balloons, rockets, and ground-based observatories. A program to enhance capabilities in these areas in preparation for the next solar maximum in 1991 is recommended. The major scientific issues are described, and required observations and coordination of observations and analyses are detailed. A program plan and conceptual budgets are provided

An Optical Study of the Circumstellar Environment Around the Crab Nebula

Long-slit spectra of two peripheral regions around the Crab Nebula show no H(alpha) emission down to a flux level of 1.5 x 10(exp -7)erg/sq cm s sr (0.63 Rayleigh), corresponding to an emission measure limit of 4.2 cm(sup - 6) pc (3(sigma)) assuming A(sub V)= 1.6(sup m) and T(sub e)=7000 K. This is below the flux levels reported by Murdin & Clark (Nature, 294, 543 (198 1)) for an H(alpha) halo around the Crab. Narrow H(beta) emission as described by Murdin (MNRAS, 269, 89 (1994)) is detected but appears to be Galactic emission unassociated with the remnant. A review of prior searches indicates no convincing observational evidence to support either a high- or low-velocity envelope around the remnant. Spectral scans confirm a well-organized, N-S expansion asymmetry of the filaments with a approx. 500 km/s central velocity constriction as described by MacAlpine et al. (ApJ, 342, 364 (1989)) and Lawrence et (it. (AJ, 109, 2635 (1995)] but questioned by Hester et al. (ApJ, 448, 240 (1995)). The velocity pinching appears to coincide with an cast-west chain of bright [O III] and helium-rich filaments. This expansion asymmetry might be the result of ejecta interaction with a disk of circumstellar matter, but such a model may be inconsistent with H and He filament abundances in the velocity constriction zone. A re-analysis of the remnant's total mass suggests that the filaments contain 4.6 +/- 1.8 M(solar) in ionized and neutral cas, about twice that of earlier estimates. For a 10M(solar) progenitor, this suggests that approx.equals 4M(solar) remains to be detected in an extended halo or wind

Nonsolar astronomy with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI)

The Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) is a NASA Small Explorer satellite designed to study hard x-ray and gamma-ray emission from solar flares. In addition, its high-resolution array of germanium detectors can see photons from high-energy sources throughout the Universe. Here we discuss the various algorithms necessary to extract spectra, lightcurves, and other information about cosmic gamma-ray bursts, pulsars, and other astrophysical phenomena using an unpointed, spinning array of detectors. We show some preliminary results and discuss our plans for future analyses. All RHESSI data are public, and scientists interested in participating should contact the principal author

Oxidative phosphorylation and lacunar stroke: Genome-wide enrichment analysis of common variants.

OBJECTIVE: We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA). METHODS: In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes. RESULTS: There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07). CONCLUSIONS: Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes.Hugh Markus is supported by an NIHR Senior Investigator award. Hugh Markus and Steve Bevan are supported by the NIHR Cambridge University Hospitals Comprehensive Biomedical Research Centre. Collection of the UK Young Lacunar Stroke Resource was primarily supported by a Functional Genomics grant from the Wellcome Trust with additional support from the Stroke Association. Genotyping and MT were supported by a project grant from the Stroke Association (TSA 2013/01). Dr. Anderson is supported by NIH-NINDS K23 NS086873 and a Fellowship in Therapeutic Investigation sponsored by the Massachusetts General Hospital Department of Neurology and Biogen Idec, Inc.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1212/WNL.000000000000226

The High Energy Solar Physics mission (HESP): Scientific objectives and technical description

The High Energy Solar Physics mission offers the opportunity for major breakthroughs in the understanding of the fundamental energy release and particle acceleration processes at the core of the solar flare problem. The following subject areas are covered: the scientific objectives of HESP; what we can expect from the HESP observations; the high energy imaging spectrometer (HEISPEC); the HESP spacecraft; and budget and schedule

Uncommon causes of ischaemic stroke: how to approach the diagnosis

Stroke is a common neurological emergency and although most cases are associated with traditional vascular risk factors leading to cerebral ischaemia by well-recognised pathophysiological mechanisms, around 4% of ischaemic strokes are due to rare conditions. These are important to recognise due to their different management, which is often specific and effective, and due to their different prognosis from otherwise cryptogenic ischaemic strokes. We outline a practical approach to identifying uncommon causes of ischaemic stroke by highlighting diagnostic 'red flags' and propose a structured approach to investigating them