Motor unit number estimation, isometric strength, and electromyographic measures in amyotrophic lateral sclerosis

Pathologic progression in amyotrophic lateral sclerosis (ALS) results from motor neuron death, while the clinical expression also reflects the compensatory effects of collateral reinnervation consequent to lower motor neuron loss. In a cross-sectional study of ALS subjects, we made comparisons between motor unit number estimation (MUNE) values and several measures reflecting collateral reinnervation, including isometric strength, compound muscle action potential (CMAP) amplitude, surface motor unit action potential (S-MUAP) amplitude, fiber density (FD), macro-EMG potential amplitude, turns-to-amplitude (T/A) ratio, and amplitude and recruitment pattern of low threshold voluntary motor units in elbow flexor muscles. Before comparisons were made, testretest reproducibility of these measures was assessed in ALS subjects, and is highest for isometric strength, and lower but similar for EMG measures. When the effects of multiple comparisons are considered, borderline significant correlations are found between MUNE values and isometric strength. Neither MUNE values nor isometric strength are significantly correlated with macro-EMG amplitude, FD, T/A ratio, or amplitude and recruitment rate of low threshold voluntary motor units. There are significant correlations of CMAP and S-MUAP with MUNE values, but these are statistical artifacts with no independent interpretation. We conclude that collateral reinnervation prevents isometric strength and EMG measures from accurately reflecting lower motor neuron death in ALS. MUNE measurements are better suited to provide insight into the true natural history of the disease process and may be clinically useful to follow progression and response in drug trials. © 1993 John Wiley & Sons, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50155/1/880161111_ftp.pd

Newborn genetic screening for spinal muscular atrophy in the UK : the views of the general population

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and a leading genetic cause of infant death worldwide. However, there is no routinescreening programme for SMA in the UK. Lack of treatments, and the inability of the screening test to accurately predict disease severity are among the key reasons screening programmes have faltered in the UK. With the recent release of the first therapy for SMA (Nusinersen) calls are being made for a reconsideration of this stance, however very little is known about the views of the general public. Methods: An online survey was administered to 232 individuals with no prior relationship to SMA to assess their attitudes towards a newborn screening programme for it. Results were compared with previously gathered data on the views of SMA families. Results: 84% of participants were in favour of newborn screening. Key reasons for support were a belief that it would lead to better healthcare and life expectancy for affected infants and facilitate informed decision-making for future pregnancies. Key reasons for non-support were a belief in the potential for significant negative impact on the family in terms of bonding and stress. Conclusions: Public acceptability is a key component in the evaluation of any potential screening programme in the UK. This study demonstrates that newborn screening for SMA is viewed largely positively by people unfamiliar with the condition. Indeed, a belief in the centrality of early identification overrode all other social and ethical concerns about screening, for the majority of participants

High-harmonic fast wave heating experiments in CDX-U

One of the primary objectives of the proposed National Spherical Tokamak Experiment (NSTX) is the investigation of very high {beta} regimes. Consequently, finding efficient methods of non-inductive heating and current drive required to heat and sustain such plasmas is of considerable importance. High-frequency fast waves are a promising candidate in this regard. However, in NSTX, the field-line pitch at the outer midplane will range from 0 up to 60 degrees from plasma start-up to current flattop. Thus, antenna strap orientation with respect to the edge magnetic field may have a serious impact on power coupling and absorption. To address this issue, the vacuum vessel of the Current Drive Experiment -- Upgrade (CDX-U) spherical tokamak has been upgraded to accommodate a rotatable two-strap antenna capable of handling several hundred kilowatts in short pulses. Details of the antenna design and results from loading measurements made as a function of power, strap angle, and strap phasing will be presented. Results from microwave scattering experiments will also be discussed

Self-organized Te redistribution during driven reconnection processes in high-temperature plasmas

Two-dimensional (2D) images of electron temperature fluctuations with high temporal and spatial resolution were employed to study the sawtooth oscillation in Toroidal EXperiment for Technology Oriented Research [S. S. Abdallaev et al., Nucl. Fusion 43, 299 (2003)] tokamak plasmas. The new findings are: (1) 2D images revealed that the reconnection is localized and permitted the determination of the physical dimensions of the reconnection zone in the poloidal and toroidal planes. (2) The combination of a pressure bulge due to finite pressure effects or a kink instability accompanied with a sharp pressure point leads to an "X-point" reconnection process. (3) Reconnection can take place anywhere along the q similar to 1 rational magnetic surface (both high- and low-field sides). (4) Heat flow from the core to the outside of the inversion radius during the reconnection time is through the finite opening on the poloidal and toroidal planes and the flow is highly collective. These new findings are compared with the characteristics of various theoretical models and experimental results for the study of the sawtooth oscillation in tokamak plasmas. (c) 2006 American Institute of Physics

Mechanical Design of the NSTX High-k Scattering Diagnostic

The NSTX High-k Scattering Diagnostic measures small-scale density fluctuations by the heterodyne detection of waves scattered from a millimeter wave probe beam at 280 GHz and {lambda}=1.07 mm. To enable this measurement, major alterations were made to the NSTX vacuum vessel and Neutral Beam armor. Close collaboration between the PPPL physics and engineering staff resulted in a flexible system with steerable launch and detection optics that can position the scattering volume either near the magnetic axis ({rho} {approx} .1) or near the edge ({rho} {approx} .8). 150 feet of carefully aligned corrugated waveguide was installed for injection of the probe beam and collection of the scattered signal in to the detection electronics

Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The ΔΔCt ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling

Differential ablation of organic coatings from micrometeoroids simulated in the laboratory

Micrometeoroids contain organic material that may undergo differential ablation during atmospheric entry, potentially depositing organic material into Earth's atmosphere and affecting the radar detectability of meteors. To investigate the differential ablation of organics, we used a dust accelerator to shoot submicron polypyrrole-coated olivine particles at speeds of 10–20 km/s into a gas target containing air. A set of biased electrodes placed along the path of the particles measured the charges generated when the particles ablated and the ablated molecules collided with gas molecules. We observed that the particles differentially ablate their organic polypyrrole coatings prior to their inorganic olivine cores, producing spikes in charge production, with charge yields of 104–105 C/kg even at relatively low speeds. These measurements suggest that large organic molecules survived ablation and are responsible for the observed charge production since small molecules either do not produce ions at those speeds or produce them in much lower quantities than observed. We modeled the ablation using basic meteor physics by assuming that the polypyrrole coating decomposes into pyrrole monomer. Extending these results to the ablation of micrometeoroids in the atmosphere indicates that organic coatings should ablate at high altitudes within relatively narrow altitude ranges, which has consequences for the detectability of meteors by radar. Since the ablated coatings generate relatively large molecules, the results also suggest that micrometeoroids can deliver complex organic material into planetary atmospheres by ablating them during entry, potentially serving as a source of prebiotic organics

Deletion of Murine SMN Exon 7 Directed to Skeletal Muscle Leads to Severe Muscular Dystrophy

Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons of the spinal cord associated with muscle paralysis and caused by mutations of the survival motor neuron gene (SMN). To determine whether SMN gene defect in skeletal muscle might have a role in SMA pathogenesis, deletion of murine SMN exon 7, the most frequent mutation found in SMA, has been restricted to skeletal muscle by using the Cre-loxP system. Mutant mice display ongoing muscle necrosis with a dystrophic phenotype leading to muscle paralysis and death. The dystrophic phenotype is associated with elevated levels of creatine kinase activity, Evans blue dye uptake into muscle fibers, reduced amount of dystrophin and upregulation of utrophin expression suggesting a destabilization of the sarcolemma components. The mutant mice will be a valuable model for elucidating the underlying mechanism. Moreover, our results suggest a primary involvement of skeletal muscle in human SMA, which may contribute to motor defect in addition to muscle denervation caused by the motor neuron degeneration. These data may have important implications for the development of therapeutic strategies in SMA