Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We ...reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with "idiopathic DBN" and thus change the aetiological spectrum.
The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests.
In 62% (n = 72) of patients the aetiology was identified ("secondary DBN"), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found ("idiopathic DBN"). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI.
Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of "idiopathic DBN" into three subgroups: "pure" DBN (n = 17); "cerebellar" DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a "syndromatic" form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration.
We present the analysis of Fermi Large Area Telescope gamma -ray observations of HB 21 (G89.0+4.7). We detect significant gamma -ray emission associated with the remnant; the flux > 100 MeV is 9.4 + ...or - 0.8 (stat) + or - 1.6 (syst) x 10 super(-11) erg cm super(-2) s super(-1). HB 21 is well modeled by a uniform disk centered at l = 88degrees.75 + or - 0degrees.04, b = +4degrees.65 + or - 0degrees.06 with a radius of 1degrees.19 + or - 0degrees.06. The gamma -ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement gamma -ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a special break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multi wavelength data favor the origin of gamma rays from nucleon-nucleon collisions. A single population of electrons cannot produce both gamma rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the gamma -ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ~3 x 10 super(49) erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ~1 x 10 super(49) erg.
The problem of eliminating divergences arising in quantum gravity is generally addressed by modifying the classical Einstein-Hilbert action. These modifications might involve the introduction of a ...local supersymmetry, the addition of terms that are higher order in the curvature to the action, or invoking compactification of superstring theory from ten to four dimensions. An alternative to these approaches is to introduce a Lagrange multiplier field that restricts the path integral to field configurations that satisfy the classical equations of motion; this has the effect of doubling the usual one-loop contributions and of eliminating all effects beyond one loop. We show how this reduction of loop contributions occurs and find the gauge invariances present when such a Lagrange multiplier is introduced into the Yang-Mills and Einstein-Hilbert actions. Moreover, we quantize using the path integral, discuss the renormalization, and then show how Becchi-Rouet-Stora-Tyutin (BRST) invariance can be used to both demonstrate that unitarity is retained and to find BRST relations between Green's functions. In the Appendices we show how background field quantization can be implemented, consider the use of a Lagrange multiplier field to restrict higher-order contributions in supersymmetric theories, and derive the BRST equations satisfied by the generating functional.
Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait ...variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (
p
< 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (
p
< 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.
Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for ...the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.
We present measurements of the relative abundances of cosmic-ray nuclei in the energy range of 500-3980 GeV/nucleon from the second flight of the Cosmic Ray Energetics And Mass balloon-borne ...experiment. Particle energy was determined using a sampling tungsten/scintillating-fiber calorimeter, while particle charge was identified precisely with a dual-layer silicon charge detector installed for this flight. The resulting element ratios C/O, N/O, Ne/O, Mg/O, Si/O, and Fe/O at the top of atmosphere are 0.919 {+-} 0.123{sup stat} {+-} 0.030{sup syst}, 0.076 {+-} 0.019{sup stat} {+-} 0.013{sup syst}, 0.115 {+-} 0.031{sup stat} {+-} 0.004{sup syst}, 0.153 {+-} 0.039{sup stat} {+-} 0.005{sup syst}, 0.180 {+-} 0.045{sup stat} {+-} 0.006{sup syst}, and 0.139 {+-} 0.043{sup stat} {+-} 0.005{sup syst}, respectively, which agree with measurements at lower energies. The source abundance of N/O is found to be 0.054 {+-} 0.013{sup stat} {+-} 0.009{sup syst+0.010esc} {sub -0.017}. The cosmic-ray source abundances are compared to local Galactic (LG) abundances as a function of first ionization potential and as a function of condensation temperature. At high energies the trend that the cosmic-ray source abundances at large ionization potential or low condensation temperature are suppressed compared to their LG abundances continues. Therefore, the injection mechanism must be the same at TeV/nucleon energies as at the lower energies measured by HEAO-3, CRN, and TRACER. Furthermore, the cosmic-ray source abundances are compared to a mixture of 80% solar system abundances and 20% massive stellar outflow (MSO) as a function of atomic mass. The good agreement with TIGER measurements at lower energies confirms the existence of a substantial fraction of MSO material required in the {approx}TeV per nucleon region.
Vestibular paroxysmia (VP), which is attributed to neurovascular cross-compression (NVCC), leads to vertiginous spells. Although VP was described more than 30 years ago by Jannetta and colleagues, we ...still need more reliable data on its diagnostic features and the efficacy of medical treatment.
A follow-up study of 32 patients with recurrent short spells of vertigo and with diagnosis of VP by published criteria was performed using medical records and patient consultation (mean follow-up time 31.3 months).
In 28% of patients the attacks occurred exclusively when at rest, whereas in 22% they were regularly precipitated by a certain action, most frequently a head turn (60%). The most common accompanying symptom was unsteadiness of stance or gait (75%). Constructive interference in steady state magnetic resonance imaging (n = 23) demonstrated at least one site of NVCC in all but one patient. Caloric testing disclosed a mild increase in vestibular deficit over time, and a hyperventilation-induced nystagmus was found in 70% of the tested patients (n = 23). The majority of patients were treated with carbamazepine (mean dose 568 mg/d) or oxcarbazepine (mean dose 870 mg/d). Treatment led to a significant reduction in the attack frequency to 10% of baseline (95% CI 6.69-14.96%), in attack intensity to 15% (95% CI 11.57-19.63%), and a reduction in attack duration to 11% (95% CI 6.72-17.40), after adjusting for time effects.
This follow-up proves the usefulness of the diagnostic criteria, especially constructive interference in steady state magnetic resonance imaging, and the therapeutic efficacy of medical treatment.
Introduction
Mal de Debarquement Syndrome (MdDS) is the rare condition of enduring rocking sensations and subjective unsteadiness following a lengthy exposure to passive motion. The pathogenesis of ...MdDS is unknown and the available treatment is limited. Here, we developed an experimental model of MdDS that may facilitate systematic inquiry of MdDS pathophysiology and the development of prevention or treatment strategies for this condition.
Methods
In an initial series of pilot experiments, suitable stimulation devices and conditions were evaluated. The final paradigm consisted of a low-frequency oscillatory motion stimulation, simultaneously deployed as roll and pitch rotation as well as heave on a six-degrees-of-freedom motion platform. Twelve healthy participants were stimulated under this condition for 30 min during free stance. Aftereffects with respect to rocking sensations and posturographic sway were monitored up to 60 min post-stimulation and compared to an initial pre-stimulation assessment as well as to posturographic recordings of spontaneous sway in ten patients with MdDS.
Results
Motion stimulation consistently evoked MdDS-like rocking sensations and postural alterations that lasted up to 45 min after cessation of passive motion exposure. Body sway alterations were most pronounced in anterior–posterior dimension during standing with eyes closed and primarily characterized by a distinct peak in the low-frequency sway spectrum close to stimulation frequency. These postural aftereffects further closely resembled spontaneous oscillatory low-frequency sway observed in patients with MdDS.
Conclusion
Subsequent neurophysiological and imaging examinations are required to investigate whether the model of transient, experimental MdDS actually shares a common substrate with the enduring pathological condition of MdDS.
Objective: To examine whether thrombolysis for stroke attributable to cervical artery dissection (CeADStroke) affects outcome and major haemorrhage rates.
Methods: We used a multicentre CeADStroke ...database to compare CeADStroke patients treated with and without thrombolysis. Main outcome measures were favourable 3‐month outcome (modified Rankin Scale 0–2) and ‘major haemorrhage’ any intracranial haemorrhage (ICH) and major extracranial haemorrhage. Adjusted odds ratios OR (95% confidence intervals) were calculated on the whole database and on propensity‐matched groups.
Results: Among 616 CeADStroke patients, 68 (11.0%) received thrombolysis; which was used in 55 (81%) intravenously. Thrombolyzed patients had more severe strokes (median NIHSS score 16 vs. 3; P < 0.001) and more often occlusion of the dissected artery (66.2% vs. 39.4%; P < 0.001). After adjustment for stroke severity and vessel occlusion, the likelihood for favourable outcome did not differ between the treatment groups ORadjusted 0.95 (95% CI 0.45–2.00). The propensity matching score model showed that the odds to recover favourably were virtually identical for 64 thrombolyzed and 64 non‐thrombolyzed‐matched CeADStroke patients OR 1.00 (0.49–2.00). Haemorrhages occurred in 4 (5.9%) thrombolyzed patients, all being asymptomatic ICHs. In the non‐thrombolysis group, 3 (0.6%) patients had major haemorrhages asymptomatic ICH (n = 2) and major extracranial haemorrhage (n = 1).
Conclusion: As thrombolysis was neither independently associated with unfavourable outcome nor with an excess of symptomatic bleedings, our findings suggest thrombolysis should not be withheld in CeADStroke patients. However, the lack of any trend towards a benefit of thrombolysis may indicate the legitimacy to search for more efficient treatment options including mechanical revascularization strategies.
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Objectives We evaluated the prevalence and mechanism of poor responsiveness to clopidogrel and prasugrel in coronary artery disease patients with and without diabetes. Background Low platelet ...inhibition by clopidogrel is associated with ischemic clinical events. A higher 600-mg loading dose (LD) has been advocated to increase responsiveness to clopidogrel. Methods In this study, 110 aspirin-treated patients were randomized to double-blind treatment with clopidogrel 600 mg LD/75 mg maintenance dose (MD) for 28 days or prasugrel 60 mg LD/10 mg MD for 28 days. Pharmacodynamic (PD) response was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The PD poor responsiveness was defined with 4 definitions previously associated with worse clinical outcomes. Active metabolites (AM) of clopidogrel and prasugrel were measured. Clopidogrel AM was added ex vivo. Results The proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo. Conclusions Prasugrel treatment results in significantly fewer PD poor responders compared with clopidogrel after a 600-mg clopidogrel LD and during MD. The mechanism of incomplete platelet inhibition in clopidogrel poor-responder groups and in diabetic patients is lower plasma levels of its AM and not differences in platelet P2Y12 receptor function.
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