Is there a difference between narrowing of the spinal canal and neurological deficits comparing Denis and Magerl classifications?

We have read with great interest the retrospective study by Caffaro and Avanzi1 evaluating the relation between narrowing of the spinal canal and neurological deficits in patients with burst-type fractures of the spine. The authors are to be commended for obtaining detailed neurological and radiological data in a large cohort of 227 patients. The authors conclude: “The percentage of narrowing of the spinal canal proved to be a pre-disposing factor for the severity of the neurological status in thoracolumbar and lumbar burst-type fractures according to the classifications of Denis and Magerl.” Although this conclusion is mainly in accordance with previous findings, we would like to comment on the methodological approach applied in the current study.

Comparison between electrically-evoked and voluntary wrist movements on sensorimotor and prefrontal cortical activation : A multi-channel time domain fNIRS study

Neuromuscular electrical stimulation (NMES) has been consistently demonstrated to improve skeletal muscle function in neurological populations with movement disorders, such as poststroke and incomplete spinal cord injury (Vanderthommen and Duchateau, 2007). Recent research has documented that rapid, supraspinal central nervous system reorganisation/neuroplastic mechanisms are also implicated during NMES (Chipchase et al., 2011). Functional neuroimaging studies have shown NMES to activate a network of sub-cortical and cortical brain regions, including the sensorimotor (SMC) and prefrontal (PFC) cortex (Blickenstorfer et al., 2009; Han et al., 2003; Muthalib et al., 2012). A relationship between increase in SMC activation with increasing NMES current intensity up to motor threshold has been previously reported using functional MRI (Smith et al., 2003). However, since clinical neurorehabilitation programmes commonly utilise NMES current intensities above the motor threshold and up to the maximum tolerated current intensity (MTI), limited research has determined the cortical correlates of increasing NMES current intensity at or above MTI (Muthalib et al., 2012). In our previous study (Muthalib et al., 2012), we assessed contralateral PFC activation using 1-channel functional near infrared spectroscopy (fNIRS) during NMES of the elbow flexors by increasing current intensity from motor threshold to greater than MTI and showed a linear relationship between NMES current intensity and the level of PFC activation. However, the relationship between NMES current intensity and activation of the motor cortical network, including SMC and PFC, has not been clarified. Moreover, it is of scientific and clinical relevance to know how NMES affects the central nervous system, especially in comparison to voluntary (VOL) muscle activation. Therefore, the aim of this study was to utilise multi-channel time domain fNIRS to compare SMC and PFC activation between VOL and NMESevoked wrist extension movements.

Peptide-functionalized polymeric nanoparticles for active targeting of damaged tissue in animals with experimental autoimmune encephalomyelitis

Increased permeability of blood vessels is an indicator for various injuries and diseases, including multiple sclerosis (MS), of the central nervous system. Nanoparticles have the potential to deliver drugs locally to sites of tissue damage, reducing the drug administered and limiting associated side effects, but efficient accumulation still remains a challenge. We developed peptide-functionalized polymeric nanoparticles to target blood clots and the extracellular matrix molecule nidogen, which are associated with areas of tissue damage. Using the induction of experimental autoimmune encephalomyelitis in rats to provide a model of MS associated with tissue damage and blood vessel lesions, all targeted nanoparticles were delivered systemically. In vivo data demonstrates enhanced accumulation of peptide functionalized nanoparticles at the injury site compared to scrambled and naive controls, particularly for nanoparticles functionalized to target fibrin clots. This suggests that further investigations with drug laden, peptide functionalized nanoparticles might be of particular interest in the development of treatment strategies for MS.

The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.

An investigation of dose calculation accuracy in intensity-modulated radiotherapy of sites in the head & neck

Knowledge of the accuracy of dose calculations in intensity-modulated radiotherapy of the head and neck is essential for clinical confidence in these highly conformal treatments. High dose gradients are frequently placed very close to critical structures, such as the spinal cord, and good coverage of complex shaped nodal target volumes is important for long term-local control. A phantom study is presented comparing the performance of standard clinical pencil-beam and collapsed-cone dose algorithms to Monte Carlo calculation and three-dimensional gel dosimetry measurement. All calculations and measurements are normalized to the median dose in the primary planning target volume, making this a purely relative study. The phantom simulates tissue, air and bone for a typical neck section and is treated using an inverse-planned 5-field IMRT treatment, similar in character to clinically used class solutions. Results indicate that the pencil-beam algorithm fails to correctly model the relative dose distribution surrounding the air cavity, leading to an overestimate of the target coverage. The collapsed-cone and Monte Carlo results are very similar, indicating that the clinical collapsed-cone algorithm is perfectly sufficient for routine clinical use. The gel measurement shows generally good agreement with the collapsed-cone and Monte Carlo calculated dose, particularly in the spinal cord dose and nodal target coverage, thus giving greater confidence in the use of this class solution.

The relationship between Bayesian motor unit number estimation and histological measurements of motor neurons in wild-type and SOD1 G93A mice

Objective: To assess the relationship between Bayesian MUNE and histological motor neuron counts in wild-type mice and in an animal model of ALS. Methods: We performed Bayesian MUNE paired with histological counts of motor neurons in the lumbar spinal cord of wild-type mice and transgenic SOD1 G93A mice that show progressive weakness over time. We evaluated the number of acetylcholine endplates that were innervated by a presynaptic nerve. Results: In wild-type mice, the motor unit number in the gastrocnemius muscle estimated by Bayesian MUNE was approximately half the number of motor neurons in the region of the spinal cord that contains the cell bodies of the motor neurons supplying the hindlimb crural flexor muscles. In SOD1 G93A mice, motor neuron numbers declined over time. This was associated with motor endplate denervation at the end-stage of disease. Conclusion: The number of motor neurons in the spinal cord of wild-type mice is proportional to the number of motor units estimated by Bayesian MUNE. In SOD1 G93A mice, there is a lower number of estimated motor units compared to the number of spinal cord motor neurons at the end-stage of disease, and this is associated with disruption of the neuromuscular junction. Significance: Our finding that the Bayesian MUNE method gives estimates of motor unit numbers that are proportional to the numbers of motor neurons in the spinal cord supports the clinical use of Bayesian MUNE in monitoring motor unit loss in ALS patients. © 2012 International Federation of Clinical Neurophysiology.