The GRAMMER European Spine Journal Award

Interdisciplinary basic research of the spine is the prerequisite to improve our understanding of back pain and spinal disorders. In order to support this spinal research, the GRAMMER European Spine Journal award (20.000 Euro) is donated annually by the companies GRAMMER AG and and Sato Office GmbH (former SID Seating GmbH) since 2000. This is the highest amount of any award in spinal research worldwide. The goal of this award is to honour outstanding research papers on the basic science of the spine. With this prize the GRAMMER company and the European Spine Journal want to award and motivate scientists from all different areas in spine research to deal with these scientific questions. Basic research in cell biology, microbiology, biochemistry, biomaterials, biomechanics, ergonomics, rehabilitation, psychology,
epidemiology, etc., provide the cornerstones for future strategies. Very often the basic science disciplines have to perform their studies with limited resources. Salaries – especially for young scientists – are often very meagre. This award attempts to acknowledge their enthusiasm and idealism.
Through this award GRAMMER is able to keep close contact with the leading, international spine scientists. The scientific exchange between these experts and GRAMMER's department of research and development improves its knowledge base, which can be directed into the development of new products.

How can this award be won?

The procedure is different from other awards. It is not necessary to submit a paper by a particular deadline to a certain committee. Each paper submitted to the European Spine Journal dealing with basic science qualifies automatically for this award as soon as it has been published. The award paper is selected by an international and interdisciplinary sub-committee of the Editorial and Advisory Board of the European Spine Journal. The winner is announced at the Annual Meeting of the Spine Society of Europe, where the certificate, together with the cheque, is presented to the authors.

Jury

At this point we would like to thank the committee for their efforts. It is not easy to make the decision, as there are always several papers which potentially qualify for the prize.

Prize winners so far

1st Grammer Award 2000 Antwerpen

Eur Spine J. 2000, 9:23-9
„Early histologic changes in lower lumbar discs and facet joints and their correlation.“

Gries NC, Berlemann U, Moore RJ, Vernon-Roberts B.

Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia.

Biomechanical and histologic studies have highlighted the close functional relationship between lumbar discs and their associated facet joints, and it is conceivable that their degenerative changes are interdependent. However, separation of cause from effect remains controversial. Hitherto, no study in humans has correlated the changes histologically. The present study assessed histologic changes in lower lumbar discs and their associated facet joints in patients under the age of 40 years using classification systems developed for this investigation. A specific objective was to correlate changes in discs and facet joints. Data from 15 lower lumbar spine specimens were obtained. Three parasagittal sections per disc and one section per facet joint were graded histologically. The results were correlated with age, within the functional spinal unit (FSU), and with the adjacent level. Histologic changes were found in discs and facet joints from all FSUs. There was no correlation between the age of the subject and the degree of degeneration of the disc or facet joints at either level. The extent of disc degeneration at L4/5 correlated significantly with changes at L5/S1 (P < 0.01). There was no correlation between changes in discs and the associated facet joints at either level. The results of the study showed that microscopic changes are seen in the disc and facet joints from an early age and can be quite marked in some individuals before the age of 40 years. A correlation of degenerative changes within the FSU could not be established.

2nd Grammer Award 2001 Göteborg

Eur Spine J. 2001;10:242-9.
„Recovery of impaired muscle function in severe sciatica.“

Balague F, Nordin M, Sheikhzadeh A, Echegoyen AC, Skovron ML, Bech H, Chassot D, Helson M.

Kanton-Hospital, Freiburg, Schweiz. balaguef@hopcantfr.ch

This is a prospective cohort study of patients with acute treated severe sciatica. The objectives of the study are, firstly, to describe the recovery of muscle performance by manual and isokinetic muscle testing in patients with acute severe sciatica over 1 year, and secondly, to discuss the potential clinical relevance of the isokinetic testing of the ankle for patients with acute sciatica. In clinical daily practice, muscle performance is evaluated by means of isometric manual tests. Different authors using manual muscle tests have reported the long-term outcome of the muscle function in patients with sciatica. Overall, the results are good in terms of the recovery of muscle strength. However, it is not clear whether the isometric strength is sufficiently relevant to evaluate the more complete muscle performance of the affected muscles in patients with sciatica. This study presents data on the muscle recovery measured with manual testing and isokinetic testing of patients with severe sciatica. Consecutive patients admitted to the Cantonal Hospital for conservative management of severe acute sciatica were eligible for inclusion in the study. Patients were evaluated at admission, discharge, and follow-up at 3, 6, and 12 months. All the visits included a standardized clinical examination and the completion of questionnaires. Imaging and electromyography were conducted at the first visit. Isokinetic muscle tests at 30 degrees/s and 120 degrees/s were performed at discharge and follow-up visits. Manual and isokinetic tests were performed on foot and ankle flexor and extensor muscles. Eighty-two consecutive patients (66% men), with a mean age of 43 (+/-10.3) years, entered the study. The prevalence of major muscle weakness was low, with 7% of patients unable to perform toe walking and 11% unable to walk on the heel at visit one. Moreover, motor deficit defined as a score of 4 or less (out of 5) was found in 15% of subjects at the first evaluation. Such severe deficits were not found during the last three visits. The isokinetic tests showed a higher prevalence of muscle function impairment. At visit 5, the isokinetic test showed impaired muscle function recovery from 23% to 32%, while the manual test showed almost full recovery. The issues of agreement between manual and isokinetic muscle testing are discussed. In this selected and homogeneous cohort of patients, the prevalence of motor deficit was rather low and the outcome excellent according to the results of the manual testing. Isokinetic muscle tests showed a higher prevalence of deficit and a much slower recovery. The manual muscle test is a crude clinical test. For more indepth muscle performance evaluation, additional testing may be necessary, especially for those patients with physically demanding jobs or activities.

3rd Grammer Award 2002 Nantes

Eur Spine J. 2001; 10:437-42
„Functional MRI of the spine: different patterns of positions of the forward flexed lumbar spine in healthy subjects.“

König A, Vitzthum HE.

Klinik und Poliklinik für Neurochirurgie der Universität Leipzig, Deutschland. koena@server3.medizin.uni-leipzig.de

Since the introduction of the technique of vertical open-configuration systems, efforts have been made to obtain functional lumbar spinal magnetic resonance (MR) images. The purpose of this study was to determine the relation between facet joint orientation and flexion patterns in the lower lumbar spine. Thirty-four normal subjects (18 women, 16 men) were examined in a vertical open 0.5-T MR scanner with T1-weighted gradient echo (GE) sequences. Flexion angles were digitally measured in the sagittal plane and facet joint orientation in the axial plane. The population showed three different functional flexion patterns: 17.6% (n=6) had kyphotic angles in all three lower lumbar levels during forward flexion (type 1), 50% (n= 17) had a lordotic angle at L5/S1 but kyphotic angles at L4/L5 and L3/L4 (type 2), and 32.4% (n=11) showed lordotic angles at L5/S1 and L4/L5 but a kyphotic angle at L3/L4 (type 3). There were statistically significant differences between flexion patterns and mean facet joint orientation: at 4/15 33.3 degrees for type 1, 33.5 degrees for type 2 and 46.2 degrees for type 3; at L5/S1 27.2 degrees for type 1, 46.4 degrees for type 2 and 48.1 degrees for type 3. There were no significant differences between the three groups at L3/L4. The three different flexion patterns in normal subjects and their relation to facet joint orientation have not been described previously. Knowledge of these patterns may lead to a better understanding of physiological spinal movement as a base for future investigations in low back pain patients.

4th Grammer Award 2003 Prag Winner 1 of 2

Eur Spine J. 2003;12:66-75.
„Induction of matrix metalloproteinase-2 and -3 activity in ovine nucleus pulposus cells grown in three-dimensional agarose gel culture by interleukin-1beta: a potential pathway of disc degeneration.“

Shen B, Melrose J, Ghosh P, Taylor F.

The Institute of Bone and Joint Research, The University of Sydney (Department of Surgery) at the Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Degeneration of the intervertebral disc is an important clinical problem, which often contributes to low back pain. Since approximately 80-90% of the general population will be subject to back pain at some stage during their lifetime, this has major socioeconomic consequences. Matrix metalloproteinases (MMPs) have been implicated in the excessive breakdown of extracellular matrix components during disc degeneration. The aim of the present study was to evaluate the regulation of MMP-2 (gelatinase-A) and MMP-3 (stromelysin) produced by cultured ovine nucleus pulposus (NP) cells stimulated with interleukin-1beta (IL-1beta). NP cells were established in three-dimensional agarose culture and stimulated with IL-1beta under serum-free conditions. Conditioned media samples were evaluated by gelatin and casein zymography and by fluorimetry using an MMP-specific substrate. Time-course and dose dependencies were established for MMP-2, -3 production by the NP cells in response to the IL-1beta. Gelatin and casein zymography indicated that elevated levels of proMMP-2 and proMMP-3 were present in media samples in response to the IL-1beta treatment. After 24-96 h culture, levels of the active 43 and 45 kDa active MMP-3 were significantly elevated, whereas MMP-2 was present mainly as its 72 kDa pro-form. Additional 36, 28 and 21 kDa MMP species were also present after prolonged incubation with IL-1beta, probably representing MMP breakdown species. IL-1beta was a potent catabolic mediator for the NP cells, resulting in the production of elevated levels of MMP-2 and -3 in culture. However, approximately 70% of the MMP-2 was present as the 72 kDa pro-form, which suggests that some additional steps are involved in its activation in vivo


4th Grammer Award 2003 Prag Winner 2 of 2

Eur Spine J. 2003 Feb;12(1):76-83. Epub 2002 Nov 22.
„Intradiscal application of hyaluronic acid in the non-human primate lumbar spine: radiological results.“

Pfeiffer M, Boudriot U, Pfeiffer D, Ishaque N, Goetz W, Wilke A.

Klinik fur Orthopadie und Rheumatologie, Philipps-Universitat, Baldingerstrasse, 35033 Marburg, Germany. michael.pfeiffer@med.uni-marburg.de

Prospectively, with randomized segment-treatment assignment, and with blinded evaluators, lumbar motion segments in Cercopithecus monkeys were analyzed for macroscopic and radiological changes 24 weeks after nucleotomy and nucleotomy with additional intradiscal application of different hyaluronic acid formulations versus untreated control segments. The objective was to find out whether hyaluronic acid is able to influence the degenerative cascade in nonhuman primates after nucleotomy. In a similar procedure, hyaluronic acid has proven to decrease degeneration after nucleotomy in a Minipig model. This is the first such study ever undertaken in primates, thus trying to overcome the known limitations of non-primate spine models. Twenty monkeys with four segments each obtained nucleotomy in three segments and solely exposure of another control segment. Nucleotomy was performed from a transpsoatic retroperitoneal approach. Preoperative radiographs and follow-up radiographs, magnetic resonance imaging (MRI), computed tomography (CT), Q-CT with bone mineral density measurements and three-dimensional reconstruction were obtained and analyzed qualitatively and quantitatively. Segments with high-molecular-weight hyaluronic acid (Hylan G-F 20) application proved to be significantly superior over those with a standard nucleotomy in radiographs, MR images, CT scans, and macroscopic appearance at follow-up. Control segments remained unaffected. Interdependence between the different methods validated the utilized methods of quantitative radiological assessment of degeneration. Hylan G-F 20 appears to be a possible adjunct in reducing postoperative degeneration in an animal nucleotomy model. It deserves further evaluation, despite the fact that the mechanisms of its effects are still speculative.

5th Grammer Award 2004 Porto

Eur Spine J. 2004 Mar;13(2):157-63. Epub 2003 Nov 14.
„Inhibition of spinal fusion by use of a tissue ingrowth inhibitor.“

Xuenong Zou, Haisheng Li, Niels Egund, Martin Lind, Cody Bunger

Orthopaedic Research Laboratory, Orthopaedic Department E, Aarhus University Hospital, Norrebrogade 44, 8000, Aarhus C, Denmark. zxnong@hotmail.com

Spinal instrumentation without fusion" techniques, which do not interfere with spinal growth, have been used extensively in the treatment of progressive spinal scoliosis in very young children. Due to subperiosteal exposure, the process of spinal instrumentation may induce spontaneous bony fusion. Instrumentation and surgical techniques have been modified in order to prevent spontaneous posterior fusion from occurring in children. An absorbable ADCON-L gel has been shown to inhibit scar and epidural adhesions following spinal surgeries. However, little is known about its influence on spinal fusion. In the present study, a single-level intertransverse arthrodesis at L4-5 on both sides was performed on each of nine pigs. Each side was randomly designed to receive autogenous bone graft with or without ADCON-L gel. The animals were followed for 10 weeks postoperatively. A fusion rate of 78% (7/9) was obtained in the autograft treatment by plain X-ray and CT evaluation, while the autograft/ADCON-L treatment yielded a 0% (0/9) fusion rate ( p = 0.001). Histomorphometric evaluation revealed that the addition of ADCON-L gel to bone graft decreased bone and bone marrow formation and significantly increased fibrous tissue formation. No statistical difference between the two treatments was found in cartilage, bone surface density, osteoid surfaces or osteoclast-covered surfaces in any zone. We conclude that ADCON-L gel mixed into autogenous bone graft can delay or decrease bone formation at spinal arthrodesis sites, thus influencing the extent of spinal fusion. This accords with our hypothesis that the use of ADCON-L gel can prevent not only the occurrence of spontaneous fusion in very young scoliosis patients after instrumentation without fusion, but also re-ossification of a decompressed spinal canal.

6th Grammer Award 2005 Barcelona

Eur Spine J. 2004 Dec;13(8):695-701. Epub 2004 Mar 27.
„Effect of nutrient deprivation on the viability of intervertebral disc cells.“

Bibby SR, Urban JP

Physiology Laboratory, Oxford University, Parks Road, Oxford OX1 3PT, UK

There is evidence that a fall in nutrient supply leads to disc degeneration but little understanding of the effects of nutrient deprivation on the physiology of disc cells which govern the composition of the disc. We examined the effects of changes in glucose and oxygen concentration and pH on the viability and metabolism of cells from bovine nucleus pulposus. Cells isolated from bovine discs and embedded in alginate beads were cultured under oxygen and glucose concentrations from zero to physiological levels and maintained at pH 7.4, pH 6.7, or pH 6.2 for up to 3 days. Interactions between nutrient concentrations were examined in relation to cell viability and lactic acid production. Cell viability was significantly reduced in the absence of glucose, with or without oxygen. Disc cells survived at 0% oxygen, provided that glucose was present, as seen previously. Cell viability decreased if the medium was acidic, more so when combined with low glucose concentrations. The rate of lactic acid production also fell as the pH became acidic and after 24 h or more at low glucose concentrations, but it did not appear to vary with oxygen concentration under the culture conditions used here. Glucose, rather than oxygen, appears to be the nutrient critical for maintaining disc cell viability. However, in an avascular tissue such as the disc, it is unlikely that glucose deprivation will occur alone; it will almost certainly correlate with a fall in oxygen concentration and pH. These results indicate that the combined nutrient and metabolite environment, rather than concentrations of any single nutrient, should be considered when studying cellular physiology in the disc.

7th Grammer Award 2006 Istanbul

Eur Spine J. 2006 Jun;15(6):764-73. Epub 2005 May 14.
„An investigation into the use of MR imaging to determine the functional cross sectional area of lumbar paraspinal muscles.“

Ranson CA, Burnett AF, Kerslake R, Batt ME, O'Sullivan PB

The purpose of this study was to investigate the use of magnetic resonance (MR) imaging and image processing software to determine the functional cross-sectional area (FCSA) (the area of muscle isolated from fat) of the lumbar paraspinal muscles. The measurement of the morphology of the lumbar paraspinal muscles has become the focus of several recent investigations into the aetiology of low back pain. However, the reliability and validity of determining the FCSA of the lumbar paraspinal muscles using MR imaging are yet to be reported. T2 axial MR scans at the L1-S1 spinal levels of six subjects were obtained using identical MR systems and scanning parameters. Lean paraspinal muscle, vertebral body bone and intermuscular fat were manually segmented using image analysis software to assign a grey scale range to the MR signal intensity emitted by each tissue type. The resultant grey scale range for muscle was used to determine FCSA measurements for each of the paraspinal muscles, psoas, quadratus lumborum, erector spinae and lumbar multifidus on each scan slice. As various biological, instrument and measurement factors can affect MR signal intensity, a sensitivity analysis was conducted to determine the error associated in calculating FCSA for paraspinal muscle using a discrete grey scale range. Cross-sectional area and FCSA measurements were repeated three times and reliability indices for the FCSA measurements were obtained, showing excellent reliability, intra class correlation coefficient (mean=0.97, range 0.90-0.99) and %SEM (mean=2.6%, range 0.7-4.8%). In addition, the error associated with miscalculation of the grey scale range for the MR signal intensity of muscle was calculated and found to be low with an error of 20 grey scale units at the upper end of the muscle's grey scale range resulting in a very small error in the measured muscle FCSA. The method presented in this paper has a variety of practical applications in areas such as evidence-based rehabilitation, biomechanical modelling and the determination of segmental inertial parameters.

8th Grammer Award 2007 Brussels

Eur Spine J. 2006 Jul;15(7):1144–9. Epub 2006 Jan 21.
„Rasterstereographic analysis of axial back surface rotation in standing versus forward bending posture in idiopathic scoliosis.“

Hackenberg L, Hierholzer E, Bullmann V, Liljenqvist U, Götze C

The forward bending test according to Adams and rib hump quantification by scoliometer are common clinical examination techniques in idiopathic scoliosis, although precise data about the change of axial surface rotation in forward bending posture are not available. In a pilot study the influence of leg length inequalities on the back shape of five normal subjects was clarified. Then 91 patients with idiopathic scoliosis with Cobb-angles between 20 degrees and 82 degrees were examined by rasterstereography, a 3D back surface analysis system. The axial back surface rotation in standing posture was compared with that in forward bending posture and additionally with a scoliometer measurement in forward bending posture. The changes of back shape in forward bending posture were correlated with the Cobb-angle, the level of the apex of the scoliotic primary curve and the age of the patient. Averaged over all patients, the back surface rotation amplitude increased from 23.1 degrees in standing to 26.3 degrees in forward bending posture. The standard deviation of this difference was high (6.1 degrees ). The correlation of back surface rotation amplitude in standing with that in forward bending posture was poor (R2=0.41) as was the correlation of back surface rotation in standing posture with the scoliometer in forward bending posture measured rotation (R (2)=0.35). No significant correlation could be found between the change of back shape in forward bending and the degree of deformity (R2=0.07), likewise no correlation with the height of the apex of the scoliosis (R2=0.005) and the age of the patient (R2=0.001). Before forward bending test leg length inequalities have to be compensated accurately. Compared to the standing posture, forward bending changes back surface rotation. However, this change varies greatly between patients, and is independent of the type and degree of scoliosis. Furthermore remarkable differences were found between scoliometer measurement of the rib hump and rasterstereographic measurement of the vertebral rotation. Therefore the forward bending test and the identification of idiopathic scoliosis rotation by scoliometer can be markedly different compared to rasterstereographic surface measurement in the standing posture.

 

9th Grammer Award 2008 Geneva

Eur Spine J 2007 Dec;16(12):2206-14. Epub 2007 Sep 21.
„Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord.“

Koda M, Kamada T, Hashimoto M, Murakami M, Shirasawa H, Sakao S, Ino H, Yoshinaga K, Koshizuka S, Moriya H, Yamazaki M

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying beta-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury.