Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia.

BACKGROUND: It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. METHODS AND RESULTS: This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3­month and P = 0.15 at 12-month follow-up). CONCLUSION: Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. CLINICAL TRIAL REGISTRATION: NTR2516.

Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients.

BACKGROUND AND PURPOSE: In chronic progressive spasticity of the legs many rare causes have to be considered, including leukodystrophies due to neurometabolic disorders. To determine the frequency of leukodystrophies and the phenotypic spectrum patients with cryptic spasticity of the legs were screened for underlying neurometabolic abnormalities. METHODS: Seventy-six index patients presenting with adult-onset lower limb spasticity of unknown cause consistent with autosomal recessive inheritance were included in this study. Screening included serum levels of very long chain fatty acids for X-linked adrenoleukodystrophy/adrenomyeloneuropathy and lysosomal enzyme activities in leukocytes for metachromatic leukodystrophy, GM1-gangliosidosis, Tay-Sachs, Sandhoff and Krabbe disease. If clinical evidence was indicative of other types of leukodystrophies, additional genetic testing was conducted. Clinical characterization included neurological and psychiatric features and magnetic resonance imaging. RESULTS: Basic screening detected one index patient with metachromatic leukodystrophy, two patients with Krabbe disease and four patients with adrenoleukodystrophy/adrenomyeloneuropathy. Additional genetic testing revealed one patient with vanishing white matter disease. These patients accounted for an overall share of 11% of leukodystrophies. One patient with Krabbe disease and three patients with adrenoleukodystrophy/adrenomyeloneuropathy presented with pure spasticity of the lower limbs, whilst one patient each with Krabbe disease, metachromatic leukodystrophy and adrenoleukodystrophy/adrenomyeloneuropathy showed additional complicating symptoms. CONCLUSIONS: Adult patients presenting with cryptic spasticity of the legs should be screened for underlying X-linked adrenoleukodystrophy/adrenomyeloneuropathy and lysosomal disorders, irrespective of the presence of additional complicating symptoms. Leukodystrophies may manifest as late as the sixth decade and hyperintensity of cerebral white matter on magnetic resonance FLAIR images is not obligatory.

Acute and Chronic Kernicterus: MR Imaging Evolution of Globus Pallidus Signal Change during Childhood.

BACKGROUND AND PURPOSE: Despite its rarity in Western countries, kernicterus resulting from severe neonatal hyperbilirubinemia and its associated neurologic consequences still persists. Subtle MR imaging patterns may be overlooked, leading to diagnostic and prognostic uncertainties. The study systematically analyzes MR imaging pattern over time. MATERIALS AND METHODS: A retrospective MR imaging study was conducted in Departments of Pediatric Neurology at the University Children's Hospitals in Leipzig, Germany, or Tübingen, Germany, between 2012 and 2022 in patients who presented beyond the neonatal period suspected of having chronic kernicterus. RESULTS: Eight patients with a total of 15 MR images were identified. The clinical diagnosis of kernicterus was confirmed in all cases on the basis of typical MR imaging findings: Bilateral, diffuse hyperintensity of the globus pallidus was observed in the neonatal period on T1WI (1 MR imaging, at 2 weeks), in infancy on T2WI (4 MR images, at 9-26 months). In children 2 years of age and older, bilateral hyperintensity on T2WI was limited to the borders of the globus pallidus (8 MR images, at 20 months -13 years). Notably, 2 children exhibited normal initial MR imaging findings at 2 months of age. Hence, MR imaging depiction of kernicterus pathology evolves with time, first evident on T1WI, subsequently on T2WI, with a "blind window" during early infancy. The T2WI signal change initially involves the entire globus pallidus and later is limited to the borders. Kernicterus had not been diagnosed in any except 2 patients by previous investigators. CONCLUSIONS: All patients presented with a characteristic clinical history and signs and an evolving MR imaging pattern. Nonetheless, the diagnosis of kernicterus was frequently missed. Abnormalities on later MR images appear to be underrecognized.

New Insights Into the Substorm Initiation Sequence From the Spatio-Temporal Development of Auroral Electrojets.

In the present study we examine three substorm events, Events 1-3, focusing on the spatio-temporal development of auroral electrojets (AEJs) before auroral breakup. In Events 1 and 2, auroral breakup was preceded by the equatorward motion of an auroral form, and the ground magnetic field changed northward and southward in the west and east of the expected equatorward flow, respectively. Provided that these magnetic disturbances were caused by local ionospheric Hall currents, this feature suggests that the equatorward flow turned both eastward and westward as it reached the equatorward part of the auroral oval. The auroral breakup took place at the eastward-turning and westward-turning branches in Events 1 and 2, respectively, and after the auroral breakup, the westward AEJ enhanced only on the same side of the flow demarcation meridian. The zonal flow divergence is considered as an ionospheric manifestation of the braking of an earthward flow burst in the near-Earth plasma sheet and subsequent dawnward and duskward turning. Therefore, in Events 1 and 2, the auroral breakup presumably mapped to the dawnward and duskward flow branches, respectively. Moreover, for Event 3, we do not find any pre-onset auroral or magnetic features that can be associated with an equatorward flow. These findings suggest that the braking of a pre-onset earthward flow burst itself is not the direct cause of substorm onset, and therefore, the wedge current system that forms at substorm onset is distinct from the one that is considered to form as a consequence of the flow braking.

Intense chorus waves are the cause of flux-limiting in the heart of the outer radiation belt.

Chorus waves play a key role in outer Van Allen electron belt dynamics through cyclotron resonance. Here, we use Van Allen Probes data to reveal a new and distinct population of intense chorus waves excited in the heart of the radiation belt during the main phase of geomagnetic storms. The power of the waves is typically ~ 2-3 orders of magnitude greater than pre-storm levels, and are generated when fluxes of ~ 10-100 keV electrons approach or exceed the Kennel-Petschek limit. These intense chorus waves rapidly scatter electrons into the loss cone, capping the electron flux to a value close to the limit predicted by Kennel and Petschek over 50 years ago. Our results are crucial for understanding the limits to radiation belt fluxes, with accurate models likely requiring the inclusion of this chorus wave-driven flux-limiting process, that is independent of the acceleration mechanism or source responsible for enhancing the flux.

Medical, psychological and intellectual development of 5-year-old children born after intracytoplasmic sperm injection.

BACKGROUND: The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. PATIENTS AND METHODS: Thus, we compared the medical and developmental outcome at a mean age of 5 years and 6 months of 35 singletons born after an ICSI procedure performed at the Tübingen Medical Center with those of 37 naturally conceived (NC) matched control singletons born at the Tübingen Medical Center. Children with congenital anomalies which could interfere with mental development were excluded, these were reported earlier. Each child was assessed neurologically and physically. Cognitive function was assessed using the Kaufman assessment battery for children (K-ABC). Behaviour was tested using a German behavioural questionnaire for preschoolers (VBV). RESULTS: Medical and cognitive outcome, and behaviour pattern were similar in both groups. Nevertheless, there were sex-related differences in favour of ICSI children: ICSI boys had better social competence than the control boys, while ICSI girls had less emotional problems than the control girls. CONCLUSIONS: Once severe congenital anomalies were excluded, there were no differences in physical and neurodevelopmental outcome of 5-year-old ICSI children compared with controls.With regard to behaviour and emotional development, ICSI children seem to be similar or might be even more stable and socially competent than the control children. As our study is limited by the small sample size, further research is needed to confirm our results.

[2-year follow-up examinations (Bayley II) in infants born at <32 weeks in a German perinatal center]. / 2-Jahres-Nachuntersuchung (Bayley) sehr kleiner Frühgeborener der Jahrgänge 2004-2007: Ergebnisse und Vollständigkeitsanalyse eines Perinatalzentrums.

BACKGROUND: Since 2008, follow-up examinations at 2 years of age with the standardized Bayley II test have become obligatory in Germany for all very low birth weight infants. AIM: We already performed such examinations before 2006. Here, we compared our data and the completeness of our examinations before and after the introduction of the obligatory 2-year follow-up. PATIENTS: From 2004-2007, 372 infants <1500 g or <32 weeks were discharged alive from our center, 19 infants died during their initial hospital stay, 2 after discharge. RESULTS: 271 patients participated in the follow-up examination at age 2 years, with the proportion of participating infants increasing from 64% to 84% after the introduction of obligatory tests. 75% of infants showed a normal development, while 4% had a severe impairment (defined as being blind (1), deaf (1) or having cerebral palsy (6), the CP rate thus being 2%). 49% of infants completed the Bayley test; the mean MDI was 100.3 (SD 10.6). There were no significant qualtitative differences in test results with the introduction of the obligatory test. CONCLUSIONS: The completeness of our follow-up increased over the years. In comparison with international data we found a low rate of severely impaired, deaf or blind VLBW infants.

Northern preference for terrestrial electromagnetic energy input from space weather.

Terrestrial space weather involves the transfer of energy and momentum from the solar wind into geospace. Despite recently discovered seasonal asymmetries between auroral forms and the intensity of emissions between northern and southern hemispheres, seasonally averaged energy input into the ionosphere is still generally considered to be symmetric. Here we show, using Swarm satellite data, a preference for electromagnetic energy input at 450 km altitude into the northern hemisphere, on both the dayside and the nightside, when averaged over season. We propose that this is explained by the offset of the magnetic dipole away from Earth's center. This introduces a larger separation between the magnetic pole and rotation axis in the south, creating different relative solar illumination of northern and southern auroral zones, resulting in changes to the strength of reflection of incident Alfvén waves from the ionosphere. Our study reveals an important asymmetry in seasonally averaged electromagnetic energy input to the atmosphere. Based on observed lower Poynting flux on the nightside this asymmetry may also exist for auroral emissions. Similar offsets may drive asymmetric energy input, and potentially aurora, on other planets.

Multi-Instrument Characterization of Magnetospheric Cold Plasma Dynamics in the June 22, 2015 Geomagnetic Storm.

We present a comparison of magnetospheric plasma mass/electron density observations during an 11-day interval which includes the geomagnetic storm of June 22, 2015. For this study we used: Equatorial plasma mass density derived from geomagnetic field line resonances (FLRs) detected by Van Allen Probes and at the ground-based magnetometer networks EMMA and CARISMA; in situ electron density inferred by the Neural-network-based Upper hybrid Resonance Determination algorithm applied to plasma wave Van Allen Probes measurements. The combined observations at L ∼ 4, MLT ∼ 16 of the two longitudinally separated magnetometer networks show a temporal pattern very similar to that of the in situ observations: A density decrease by an order of magnitude about 1 day after the Dst minimum, a partial recovery a few hours later, and a new strong decrease soon after. The observations are consistent with the position of the measurement points with respect to the plasmasphere boundary as derived by a plasmapause test particle simulation. A comparison between plasma mass densities derived from ground and in situ FLR observations during favorable conjunctions shows a good agreement. We find however, for L < âˆ¼3, the spacecraft measurements to be higher than the corresponding ground observations with increasing deviation with decreasing L, which might be related to the rapid outbound spacecraft motion in that region. A statistical analysis of the average ion mass using simultaneous spacecraft measurements of mass and electron density indicates values close to 1 amu in plasmasphere and higher values (∼2-3 amu) in plasmatrough.

Metachromatic leukodystrophy--an update.

Metachromatic leukodystrophy (MLD) is a rare lysosomal sphingolipid storage disorder, caused by a deficiency of arylsulfatase A (ASA). It is inherited in an autosomal recessive way, among Caucasians three causing alleles are frequent. Demyelination is the hallmark of MLD. Interest in the disease has increased as therapeutic options such as stem cell transplantation, enzyme replacement and gene therapy are topics of current research. A late-infantile (onset before 3 years of age), a juvenile form (onset before 16 years) and an adult form are usually distinguished. Rapid motor decline is typical for the first and also the second forms, the second may be preceded by cognitive and behavioural problems, which mainly characterize the adult form. There is evidence for a genotype-phenotype correlation: patients homozygous for alleles which do not allow the expression of any enzyme activity (null-allele) suffer from the late infantile form; heterozygosity for a null allele and a non-null allele are more associated with the juvenile form and homozygosity for non-null alleles is more frequent in the most attenuated adult onset form.

Ulysses dust measurements near Jupiter.

Submicrometer- to micrometer-sized particles were recorded by the Ulysses dust detector within 40 days of the Jupiter flyby. Nine impacts were recorded within 50 Jupiter radii with most of them recorded after closest approach. Three of these impacts are consistent with particles on prograde orbits around Jupiter and the rest are believed to have resulted from gravitationally focused interplanetary dust. From the ratio of the impact rate before the Jupiter flyby to the impact rate after the Jupiter flyby it is concluded that interplanetary dust particles at the distance of Jupiter move on mostly retrograde orbits. On 10 March 1992, Ulysses passed through an intense dust stream. The dust detector recorded 126 impacts within 26 hours. The stream particles were moving on highly inclined and apparently hyperbolic orbits with perihelion distances of >5 astronomical units. Interplanetary dust is lost rather quickly from the solar system through collisions and other mechanisms and must be almost continuously replenished to maintain observed abundances. Dust flux measurements, therefore, give evidence of the recent rates of production from sources such as comets, asteroids, and moons, as well as the possible presence of interstellar grains.

Cerebral manifestation of Wilson's disease successfully treated with liver transplantation.

The main indication for orthotopic liver transplantation (OLTx) in Wilson's disease (WD) is severe hepatic decompensation. Our 15-year-old patient is the second case to date in whom OLTx was performed because of neurologic manifestations resulting from WD. His initial condition involving recurrent headaches, tremor, and athetoid hand movements progressively deteriorated during therapy with D-penicillamine, zinc sulfate, and trientine until he was severely dysarthric, unable to walk, and bedridden. After OLTx, his neurologic condition became almost normal.

Early left periventricular brain lesions induce right hemispheric organization of speech.

Right-hemispheric organization of speech has been observed following early left-sided brain lesions involving the language cortex. The authors studied speech organization in hemiparetic patients with pre- and perinatally acquired lesions in the left periventricular white matter using fMRI, and found that right-hemisphere activation correlated with left facial motor tract involvement. This suggests that the impairment of speech motor output from the left hemisphere plays an important role in this alteration of language representation.

Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy.

OBJECTIVE: To report three unrelated infants with a distinctive phenotype of Leigh-like syndrome, neurogenic muscular atrophy, and hypertrophic obstructive cardiomyopathy. The patients all had a homozygous missense mutation in SCO2. BACKGROUND: SCO2 encodes a mitochondrial inner membrane protein, thought to function as a copper transporter to cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. Mutations in SCO2 have been described in patients with severe COX deficiency and early onset fatal infantile hypertrophic cardioencephalomyopathy. All patients so far reported are compound heterozygotes for a missense mutation (E140K) near the predicted CxxxC metal binding motif; however, recent functional studies of the homologous mutation in yeast failed to demonstrate an effect on respiration. METHODS: Here we present clinical, biochemical, morphologic, functional, MRI, and MRS data in two infants, and a short report in an additional patient, all carrying a homozygous G1541A transition (E140K). RESULTS: The disease onset and symptoms differed significantly from those in compound heterozygotes. MRI and muscle morphology demonstrated an age-dependent progression of disease with predominant involvement of white matter, late appearance of basal ganglia lesions, and neurogenic muscular atrophy in addition to the relatively late onset of hypertrophic cardiomyopathy. The copper uptake of cultured fibroblasts was significantly increased. CONCLUSIONS: The clinical spectrum of SCO2 deficiency includes the delayed development of hypertrophic obstructive cardiomyopathy and severe neurogenic muscular atrophy. There is increased copper uptake in patients' fibroblasts indicating that the G1541A mutation effects cellular copper metabolism.

The Rett syndrome: magnetic resonance imaging and clinical findings in four girls.

The clinical and laboratory findings in 4 girls with the Rett syndrome are presented. The MRI results at different disease stages with detailed descriptions of the techniques applied-including quantification of T1 and T2 relaxation times in the brain-are reported. There were no pathological signal intensities in T1- or T2-weighted images. Thus, MRI does not provide any significant additional help in the diagnosis of the Rett syndrome. However, it does indicate that disturbances of myelinization or the brain water content are not probable etiologies in this syndrome.

Assessment and therapy monitoring of Leigh disease by MRI and proton spectroscopy.

In a 2-year-old boy with Leigh disease, spasticity, dysarthria, and optic atrophy gradually developed. Computed tomography and magnetic resonance imaging disclosed progressive, symmetric basal ganglia lesions. In muscle tissue, a defect of pyruvate dehydrogenase complex was found. Magnetic resonance volume selective proton spectroscopy (MRVS) of the basal ganglia demonstrated an abnormal lactate peak. A ketonemic diet coincided with clinical stabilization and arrest of progressive brain lesions. Lactate could no longer be demonstrated by MRVS. It reappeared with a new brain lesion coinciding with discontinuation of the diet. MRVS, therefore, appears to be a sensitive tool to evaluate pathologic lactate production in metabolic brain disease with disturbed energy metabolism and allows noninvasive therapy monitoring.

Transitory neurological findings in a population of at risk infants.

Two-hundred fifty infants with high and no risk history transitory neurological findings (TNF) were examined during the first year of life. The neurological situation and the developmental progress were reconsidered in these children at 2.5-4.5 and 5-7 years of age. TNF were diagnosed mainly during the first two trimesters. Hyperirritability and asymmetries resolved to about 70% during the first half of the first year of life. In contrast, isolated central hypotonia resolved over a much longer period. No correlations of distinct types of TNF could be found with VLBW and LBW-infants, with fullterm infants, with birthweights, nor with risk factors. Children who developed spastic CP presented permanent hypertonia beside other specific neurological symptoms during the second half of the first year of life. Children with lasting non-spastic handicaps showed permanent hypotonia combined with other neurological abnormalities and symptoms of psychomotor retardation, which evolved also during the second half of the first year. From these results the question arises: which parts of TNF are essentially neurobiological findings indicating processes of transformation of the sensory motor system from non-intentional fetal to intentional motor behaviour of early infancy. TNF, then, should not longer be looked at as symptoms of pathological value only.

[Normal myelination in childhood brains using MRI--a meta analysis]. / Die normale Myelinisierung des kindlichen Gehirns in der MRT--eine Metaanalyse.

PURPOSE: To establish age limits for the assessment of normal myelination of the brain on T1-weighted (T1w) and T2-weighted (T2w) images. METHOD: Comparison of previous publications (Barkovich et al. 1988, Grodd 1993, Hayakawa et al. 1990, Hittmair et al. 1994, Martin et al. 1988/1990/1991, Nakagawa et al. 1998, Staudt et al. 1993/1994, Stricker et al. 1990). RESULTS: Despite technical and methodological differences, these studies principally agreed on the timing of myelination for most regions of the brain. Thus, a common time-table could be established: At 1 month, myelin is visible on both T1w and T2w in the medulla oblongata, tegmentum pontis, cerebellar peduncles and vermis, quadrigeminal plate, decussation of superior cerebellar peduncles, thalamus, posterior limb of internal capsule, optic radiation, corona radiata. Thereafter, the myelin-typical signal in the different regions of the brain should be present at the following ages (M = months): anterior limb of internal capsule (2 M: T1w; 7 M: T2w), splenium of corpus callosum (4 M: T1w; 6 M: T2w), genu of corpus callosum (6 M: T1w; 8 M: T2w), centrum semiovale (2 M: T1w; 7 M: T2w). Branching of myelin into the gyri of the telencephalon (= arborization) appears at the latest at: occipital lobe (5 M: T1w; 12 M: T2w) and frontal lobe (7 M: T1w; 14 M: T2w). CONCLUSION: These extracted age limits can be used for a more reliable assessment of myelination than the time-tables from a single study.

Morphological determination of the age of Cysticercus bovis in very young calves with cysticercosis.

Characteristics and measurements are given for early developmental stages of Cysticercus bovis. The data emerging from our study indicate that the age of a one to two month-old larva from a spontaneous infection can reliably be determined in histological sections. On these grounds we have been able to determine that the cysticercus infection in the two calves (aged 21 and 27 days respectively) had been acquired prenatally.

Relationships among cognitive complexity, sex, and spatial task performance in college students.

This study examined the relationship between object differentiation (spatial ability) and social differentiation (cognitive complexity). Prior research had demonstrated a link between field independence and cognitive complexity, and between field independence and spatial ability. This raises the question whether some unitary cognitive style is involved in both spatial ability and cognitive complexity. The present study used a spatial task (a variation of Piaget & Inhelder's water level task) and several measures of cognitive complexity (the Barron Complexity scale, Intolerance of Ambiguity scale, and measures of self-differentiation and differentiation of other persons) to test the prediction that complexity will be positively related to performance on the water level task. On the basis of earlier findings, we also predicted that males would outperform females on the water level task. Thirty-eight male and 98 female undergraduates completed the water level task and the complexity measures. Results confirmed the predictions, except that the relationship between cognitive complexity and performance was different for males than for females. For males, the correlations between scores on the water level task and the several measures of complexity were considerably higher than for females. Such results suggest that for males spatial task performance can be related to a general construct such as cognitive style; for females, this does not appear to be the case.