Does the Neurological Examination Correlate with Patient-Perceived Outcomes in Degenerative Cervical Myelopathy?

BACKGROUND: In patients with neurological disorders, a divergence can exist between patients' perceptions regarding the outcomes and the objective neurological findings. Degenerative cervical myelopathy (DCM), a prevalent condition characterized by progressive compression of the cervical spinal cord, can produce debilitating symptoms and profound neurological findings. The purpose of the present study was to determine whether the physician-derived neurological examination findings, as recorded by American Spine Injury Association (ASIA) summary score, correlated with the patient-derived outcome measures for DCM. METHODS: A total of 78 patients underwent surgical management of DCM with completion of preoperative and 6-month follow-up assessments. Surgical management consisted of either anterior or posterior cervical decompression. All patients underwent a neurological evaluation, including an ASIA assessment before surgery and 6 months after surgery, and completed the modified Japanese Orthopaedic Association (mJOA), neck disability index (NDI), and Short-Form 36-item (SF-36) scales pre- and postoperatively to measure both disease-specific and general perceived outcomes. RESULTS: The objective physician-derived neurological testing (ASIA) did not correlate with the patient-derived scales (mJOA, NDI, and SF-36) pre- or postoperatively. Patients reported significant improvements (P < 0.001) at 6 months postoperatively in extremity functioning (mJOA), neck pain (NDI), overall physical health (SF-36), and objective strength and sensory functioning (ASIA). All patient-perceived outcome measures correlated with each other pre- and postoperatively (P < 0.01). CONCLUSIONS: Objective scoring of postoperative neurological function did not correlate with patient-perceived outcomes before and after surgery for DCM. Traditional testing of motor and sensory function as part of the neurological assessment may not be sensitive enough to assess the scope of neurological changes experienced by patients with DCM.

Cervical Spondylotic Myelopathy: Metabolite Changes in the Primary Motor Cortex after Surgery.

Purpose To characterize longitudinal metabolite alterations in the motor cortex of patients with cervical spondylotic myelopathy (CSM) by using proton magnetic resonance (MR) spectroscopy and to evaluate white matter integrity with diffusion-tensor imaging in patients who are recovering neurologic function after decompression surgery. Materials and Methods Informed written consent was obtained for all procedures and the study was approved by Western University's Health Sciences Research Ethics Board. Twenty-eight patients with CSM and 10 healthy control subjects were prospectively recruited and underwent two separate 3-T MR imaging examinations 6 months apart. Patients with CSM underwent surgery after the first examination. N-acetylaspartate (NAA), an indicator of neuronal mitochondrial function, normalized to creatine (Cr) levels were measured from the motor cortex contralateral to the greater functional deficit side in the patient group and on both sides in the control group. Fractional anisotropy and mean diffusivity were measured by means of diffusion-tensor imaging in the white matter adjacent to the motor and sensory cortices of the hand and the entire cerebral white matter. Clinical data were analyzed by using Student t tests. Results In patients with CSM, NAA normalized to Cr (NAA/Cr) levels were significantly lower 6 months after surgery (1.48 ± 0.08; P < .03) compared with preoperative levels (1.73 ± 0.09), despite significant improvement in clinical questionnaire scores. Fractional anisotropy and mean diffusivity were the same (P > .05) between the patient and control groups in all measured regions at all time points. Conclusion NAA/Cr levels decreased in the motor cortex in patients with CSM 6 months after successful surgery. Intact white matter integrity with decreased NAA/Cr levels suggests that mitochondrial metabolic dysfunction persists after surgery. © RSNA, 2016 Online supplemental material is available for this article.

Loss of potassium homeostasis underlies hyperthermic conduction failure in control and preconditioned locusts.

At extreme temperature, neurons cease to function appropriately. Prior exposure to a heat stress (heat shock [HS]) can extend the temperature range for action potential conduction in the axon, but how this occurs is not well understood. Here we use electrophysiological recordings from the axon of a locust visual interneuron, the descending contralateral movement detector (DCMD), to examine what physiological changes result in conduction failure and what modifications allow for the observed plasticity following HS. We show that at high temperature, conduction failure in the DCMD occurred preferentially where the axon passes through the thoracic ganglia rather than in the connective. Although the membrane potential hyperpolarized with increasing temperature, we observed a modest depolarization (3-6 mV) in the period preceding the failure. Prior to the conduction block, action potential amplitude decreased and half-width increased. Both of these failure-associated effects were attenuated following HS. Extracellular potassium concentration ([K+]o) increased sharply at failure and the failure event could be mimicked by the application of high [K+]o. Surges in [K+]o were muted following HS, suggesting that HS may act to stabilize ion distribution. Indeed, experimentally increased [K+]o lowered failure temperature significantly more in control animals than in HS animals and experimentally maintained [K+]o was found to be protective. We suggest that the more attenuated effects of failure on the membrane properties of the DCMD axon in HS animals is consistent with a decrease in the disruptive nature of the [K+]o-dependent failure event following HS and thus represents an adaptive mechanism to cope with thermal stress.

Monoclonal antibodies to elongation factor-1alpha inhibit in vitro translation in lysates of Sf21 cells.

Elongation factor-1alpha (EF-1alpha) is an enzyme that is essential for protein synthesis. Although EF-1alpha offers an excellent target for the disruption of insect metabolism, agents known to interfere with EF-1alpha activity are toxic to humans. In this article, we describe the development of monoclonal antibodies (MAbs) that can disrupt the activity of insect EF-1alpha without cross-reacting with the human enzyme. MAbs were generated to EF-1alpha from Sf21 cells derived from the fall armyworm, Spodoptera frugiperda, by immunizing mice with EF-1alpha eluted from SDS-PAGE gels. The MAbs reacted with EF-1alpha in eggs and first through fifth instars of the fall armyworm in immunoblots of SDS-PAGE gels, but did not recognize EF-1alpha in human carcinoma cells and normal tissues. MAbs with the ability to recognize EF-1alpha in its native conformation, identified through immunoprecipitation experiments, were added to Sf21 cell lysates to determine whether the antibodies could inhibit incorporation of [(35)S]methionine into newly synthesized in vitro translation products. Of the four EF-1alpha-specific MAbs tested, three significantly inhibited protein synthesis when compared to the negative control antibody (P < 0.001, one-way ANOVA; followed by Dunnett's test, P < 0.05).

An antibody diagnostic for hymenopteran parasitism is specific for a homologue of elongation factor-1 alpha.

An enzyme-linked immunosorbent assay (ELISA) useful for identifying noctuid pests parasitized by hymenopteran endoparasitoids was recently described. The ELISA employed a monoclonal antibody (MAb 9A5) that appeared highly polyspecific for parasitoid antigens, yielding banding patterns more typical of a polyclonal antiserum than of a monoclonal antibody in immunoblots of parasitoid homogenates subjected to SDS-PAGE. Although MAb 9A5 appeared capable of binding to dozens of parasitoid antigens, no cross-reactivity for noctuid antigens was evident by either immunoblotting or ELISA. In the study described here, immunoprecipitation, SDS-PAGE, and N-terminus amino acid sequencing were used to identify the protein recognized by MAb 9A5 as a homologue of elongation factor-1 alpha (EF-1 alpha). The propensity for EF-1 alpha to bind to cytoskeletal components, the additional subunits of EF-1, and other proteins may account for the apparent polyspecificity of MAb 9A5 in immunoblots of whole-body parasitoid homogenates. The presence of a unique hymenopteran epitope suggests that EF-1 alpha molecules from other insect groups could similarly express novel determinants. These determinants may prove useful not only for insect detection, but also as targets for selective insecticides that act by inhibiting protein synthesis.

Physiological correlates to 800 meter running performance.

Much of the previous research efforts aimed at determining those physiological characteristics that contribute to distance running success have centered around distances greater than 1500 meters with little attention to events such as the 800 meter run. Therefore, this investigation examined the relationship between selected physiological and body composition, characteristics and performance in an 800 meter run. Measurements of body composition, VO2max, running economy, and performance times for 100 and 300 meter dashes were obtained on 11 male track athletes. Stepwise multiple regression analysis was performed using 800 meter race time as the dependent variable. Although the combination of 300 and 100 meter run times, percent body fat, running economy and VO2 max as independent variables accounted for the greatest amount of total variance (r2 = .89), the additional variance explained by the model did not increase significantly (p greater than 0.05), when VO2max, percent body fat, and running economy were added to a model which contained 300 and 100 meter run time (r2 = .85) as the explanatory variables. These data offer additional support for the notion that much of the intramuscular ATP produce and utilized during an 800 meter run comes from anaerobic metabolic pathway.

Monoclonal IgM rheumatoid factor-like anti-globulins enhance the inhibitory effects of Plasmodium falciparum-specific monoclonal antibodies in vitro.

Monoclonal IgM rheumatoid factor-like anti-globulins were produced by in vitro stimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites of Plasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas. In vitro, these anti-globulins augmented the inhibitory effects of P. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti-globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases.

Hemoglobin desaturation in highly trained athletes during heavy exercise.

It has been generally accepted that during exercise at sea level, the pulmonary system of normal, healthy individuals is capable of maintaining arterial oxygen tension at near resting levels. However, recent evidence questions whether this generalization applies to the highly trained endurance athlete who is capable of achieving very high levels of metabolic demand. Hence, the purpose of these experiments was to examine the relationship between maximal oxygen consumption (VO2max) and arterial oxygen-hemoglobin saturation (%SaO2) during short-term heavy exercise in trained athletes and untrained individuals. Ten trained distance runners and 7 untrained males exercised at 95% of VO2max for 3 min. Minute-by-minute measurement of %SaO2 was obtained via ear oximetry. The correlation coefficients between %SaO2 and VO2max during exercise were r = -0.68, r = -0.74, and r = -0.72 (P less than 0.05) for minutes 1 through 3, respectively. In general those individuals with the highest VO2max showed the greatest decrease in %SaO2. By comparison there was no difference (P greater than 0.05) in resting %SaO2 between the trained (96.3 +/- 0.2% [SE]) and the untrained (96.3 +/- 0.4%) subjects. However, at minute 3 of exercise, %SaO2 was significantly lower (P less than 0.05) in the trained subjects (87.0 +/- 0.7%) than in the untrained subjects (92.6 +/- 0.7%). These data demonstrate that arterial desaturation occurs in healthy, highly trained endurance athletes during heavy exercise and that the level of the arterial desaturation is inversely related to VO2max.

Peak oxygen uptake in arm ergometry: effects of testing protocol.

The purpose of this investigation was to determine if a new proposed arm ergometer protocol was advantageous in eliciting higher peak oxygen uptake (peak VO2) when compared with two protocols currently referred to in the literature. Ten male subjects were tested on three different exercise protocols; a discontinuous test (DT), a continuous test (CT) and a new proposed jump-max test (JMT). The CT began at a work rate of 33 watts (W) (40 rpm) with the power output (PO) being increased 16 W every 3 minutes. The DT began without resistance on the ergometer flywheel (50 rpm) and the work rate was increased by 25 W every 3 minutes with a 1-minute rest between stages. The JMT began with a 3-minute pretest to determine a PO which elicited a HR of 120 +/- 5 beat min-1. After a 2-minute rest, subjects began exercise at the predetermined work rate (80 rpm) with the PO being increased 20 W each minute of the test. Oxygen uptake was measured minute by minute via open circuit spirometry. Peak VO2 was higher (p less than 0.05) in the JMT (mean +/- SEM = 2.36 +/- 0.06 l.min-1) when compared with either (means +/- SEM = 2.16 +/- 0.07 l.min-1) or the CT (means +/- SEM = 2.04 +/- 0.10 l.min-1). No difference (p greater than 0.05) existed in peak VO2 between the CT and the DT. These data suggest that the proposed JMT may result in a higher measured peak VO2 in subjects when compared with either DT or CT of moderate to long duration.

Efficiency of trained subjects differing in maximal oxygen uptake and type of training.

This study was undertaken to examine the relationship between energy expenditure and work rate on a bicycle ergometer in five sprinters and five distance runners who differed in maximal oxygen uptake (VO2max) and type of training. Each subject performed at work rates of 30, 60, 90, 120, and 150 watts (W). The relationship between energy expenditure and work rates was most accurately described by a quadratic curve for both groups: for sprinters, energy expenditure (kJ) = 11.57 + 0.1812 (W) + 0.00046 (W)2; for distance runners, energy expenditure (kJ) = 11.74 + 0.1386 (W) + 0.00060 (W)2. Delta efficiency (delta work accomplished divided by delta energy expended X 100%) decreased as work rate increased. Statistical analyses revealed no significant differences between groups in delta efficiency at the same work rate (P greater than 0.25) or at the same relative work rate (P greater than 0.75). These results suggest that differences in VO2max and/or type of training have little or no causal effect on the decrease in delta efficiency with increasing work rate. The observed decrease in delta efficiency may be due to increases in metabolism not directly related to the performance of the external work or to an increasing amount of unmeasured work as work rate increases on a bicycle ergometer.