Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.

The Franco-Canadian multicolumn spinal cord stimulation prospective study: a subgroup analysis focusing on the decisive role of lead positioning.

INTRODUCTION: Multicolumn spinal cord stimulation (SCS) is now considered to be effective for the treatment of the radicular and back component in refractory Failed Back Surgery Syndrome (FBSS) patients. The relationship between the paresthesia coverage of the back and clinical outcomes has recently been confirmed by an international prospective study. However, significant disparities in outcomes were identified and could result from the heterogeneity of lead implantation parameters which are dependant on local practices and experience. We therefore sought to analyse the impact of lead implantation level and its lateralization on the ability to address back pain with multicolumn SCS leads. STUDY OBJECTIVES, MATERIALS AND METHODS: The present study was a retrospective subgroup analysis from an observational, prospective non-randomized trial that included 76 patients with refractory FBSS, implanted with multicolumn SCS between 2008 to 2011 in three neurosurgical pain centres (Poitiers, France, Montreal, Canada and Regina, Canada). A subgroup of 21 patients with "optimized lead positioning" (OLP) was identified, distinguished from the rest of the main study population (NON OLP subgroup; n=51) and submitted to specific data analysis. Baseline characteristics of both groups were strictly comparable. Our primary objective was to analyse the impact of lead positioning (vertebral level and lateralization) on the back paresthesia coverage. The secondary objectives were to compare the analgesic and functional efficacy of multicolumn stimulation in these OLP and NON OLP subgroups and to determine if a paresthesia coverage improvement leads to better clinical outcomes in these difficult-to-treat patients. RESULTS: In this subgroup analysis, unilateral coverage of the low back area was achieved in 85.0% of OLP patients vs. 76.5% in the NON OLP group. Bilateral and complete coverage of the low back area was achieved in 60% of OLP patients vs. 51% in the NON OLP group but these differences were not statistically significant. At 6months, 81.0% of OLP patients vs. 69.4% in the NON OLP group presented at least 30% improvement of the low back VAS, while 52.4% of them achieved at least 50% improvement of the low back VAS vs. 38.8% in the NON OLP group. Functional improvement at 6months, available and calculated only in the French group of OLP patients (n=14) by the Oswestry Disability Index, was significant, decreasing from 60.67% to 33.43%. CONCLUSION: Despite limitations in this retrospective subgroup analysis, this study suggests that the vertebral level (T8-T9) and midline positioning of the lead during implantation could be decisive factors to optimize paresthesia coverage and finally, clinical and functional outcomes. While sophistication has been responsible for an increase of the size and the programming possibilities of surgical SCS leads during the past years, multicolumn SCS lead implantation should in fact be considered as a "functional neurosurgical" procedure and could benefit from intraoperative patient cooperation, as in the case for deep brain stimulation procedures, due to minimally invasive implantation techniques.

Docosahexaenoic acid (DHA) injection in spinal cord transection stimulates Na⁺,K⁺-ATPase in skeletal muscle via ß 1 subunit.

Spinal cord injuries (SCI) induce a loss of skeletal muscle mass and functional capacity. The muscle excitability and contractility depend on the plasma membrane potential, regulated by transmembrane ion gradients, and thus necessarily on the Na⁺,K⁺-ATPase activity. The aim of this work was to evaluate the consequences of a spinal cord transection (SCT) on the skeletal muscle Na⁺,K⁺-ATPase and the impact of collateral GlyceroPhosphoLipids enriched in DocosaHexaenoic Acid (GPL-DHA) administration. The Na⁺,K⁺-ATPase activity and membrane expression of Na⁺,K⁺-ATPase α1, α2 and ß1 isoforms were assessed by K⁺-stimulated paranitrophenyl phosphatase (pNPPase) measurements and Western Blotting, respectively. The results show that spinal cord transection increased significantly (p<0.05) Na⁺,K⁺-ATPase activity in muscle by 25% and decreased the amounts of α1 isoform and α2 isoform expressions by 50% (p<0.05) respectively compared to controls. The results also show that early injection of GPL-DHA after SCT decreases in membrane skeletal muscle the α1 and α2 isoforms expression but increases the membrane Na⁺,K⁺-ATPase activity. This treament partially restores the membrane expression of the ß1 subunit of the Na⁺,K⁺-ATPase. These data suggest that the increase of ß1 subunit expression is probably the main trigger to the membrane Na⁺,K⁺-ATPase activation following a trans-synaptic denervation.

Protein multi-scale organization through graph partitioning and robustness analysis: application to the myosin-myosin light chain interaction.

Despite the recognized importance of the multi-scale spatio-temporal organization of proteins, most computational tools can only access a limited spectrum of time and spatial scales, thereby ignoring the effects on protein behavior of the intricate coupling between the different scales. Starting from a physico-chemical atomistic network of interactions that encodes the structure of the protein, we introduce a methodology based on multi-scale graph partitioning that can uncover partitions and levels of organization of proteins that span the whole range of scales, revealing biological features occurring at different levels of organization and tracking their effect across scales. Additionally, we introduce a measure of robustness to quantify the relevance of the partitions through the generation of biochemically-motivated surrogate random graph models. We apply the method to four distinct conformations of myosin tail interacting protein, a protein from the molecular motor of the malaria parasite, and study properties that have been experimentally addressed such as the closing mechanism, the presence of conserved clusters, and the identification through computational mutational analysis of key residues for binding.

Parametric sensitivity analysis and reduction of a detailed nutritional model of plant cell cultures.

A kinetic model of plant nutrition described by Cloutier et al. (Cloutier et al., 2008. Biotechnol Bioeng 99:189-200) is progressively simplified so as to obtain a predictive model that describes the evolution of the biomass and the extracellular and intracellular concentrations of three determining nutrients, that is, free intracellular nitrogen, phosphate, and carbohydrate compounds. Three techniques of global sensitivity analysis are successively applied to assess the model parameter influence and potential correlation. The resulting dynamic model is able to predict plant growth for the two most encountered plant bioprocesses, namely suspension cells and hairy roots.

[The main tunnel syndromes]. / Les principaux syndromes canalaires.

Several tunnel syndromes are responsible for substantial functional impairment. The diagnosis has to be made and treatment is most often very simple--nerve decompression--with excellent results. Of these syndromes, the most common are median and ulnar tunnel syndromes of the wrist and ulnar tunnel syndrome of the elbow, but other syndromes must be identified at the risk of therapy failure due to poorly adapted treatment. Finally, good knowledge of this pathology must lead to prevention of the iatrogenic forms (sequelae of inguinal hernia treatment, ileac crest graft harvesting) by educating all surgeons interested in peripheral nerve surgery.

[Anatomic bases of surgical approaches to the nerves of the lower limb: tips for young surgeons]. / Bases anatomiques des voies d'abord chirurgicales des nerfs du membre inférieur: à l'usage des jeunes neurochirurgiens.

For trainee surgeons, the surgical approaches of the lower limb's peripheral nerves remain partially or completely unknown, but traumatic nerve lesions are rather frequent at this level and nerve tumors require intervention. Young surgeons will also have to treat spasticity and perform selective neurotomies, which can provide dramatic improvement of the functional status of properly selected patients. Excellent knowledge of anatomy is the key point to successful surgery. For each nerve approach, the key points on the morphological data of the nerve and its surroundings are given, as are the typical indications for this surgery and certain particularities related to patient installation in the operating room. The surgical approach section details the incision, the nerve exposure and the technical pitfalls.

[Anatomic bases of surgical approaches to the nerves of the upper limb: tips for young surgeons]. / Bases anatomiques des voies d'abord chirurgicales des nerfs du membre supérieur: à l'usage des jeunes neurochirurgiens.

Peripheral nerve surgery requires a certain level of specialization. Surgeons must have solid knowledge of morphological anatomy of the different segments to be explored, decompressed, repaired, or even neurotized. This paper describes the most common approaches to the peripheral nerves of the upper limb.

[Physiology of the injured peripheral nerve]. / Physiologie du nerf traumatisé.

Peripheral nerve injuries are frequent and generate significant deficits. Their treatment sometimes leads to functional recovery but is mostly incomplete or unpredictable, despite the regular use of sophisticated repair techniques. The clinician must clearly understand the peripheral nervous system's responses to injury, which reveal surprising degenerating and spontaneous regenerating abilities. This potential recovery is a peripheral nervous system specificity and follows a relatively complex process. Peripheral neurons depend on glial cell structure and metabolism, inducing a global and dynamic response of the whole axon environment, even in cases of focal lesion, modulated by the initial type and mechanism of injury. Today's progress remains insufficient to improve functional prognosis significantly, but a better understanding of peripheral nerve regenerating processes has opened the door to new medical and surgical advances.

Increased arterial calcification in Paget's disease of bone.

When examining radiographs of patients with Paget's disease of bone (PD), we often observed calcification of the aorta and iliac or femoral arteries. The processes of extraosseous calcification or mineralization are very close to the mechanisms regulating mineralization of bone tissue. The aim of our study was to quantify the number, extent (length and thickness), and type (arteriosclerotic or medial arterial calcification) of vascular calcification in patients with Paget's disease and to compare them with those of controls, in order to discover whether PD is accompanied by increased calcification. Vascular calcification was quantified on the aorta, the iliac arteries, and their branches, the femoral, gluteal, and pelvic arteries of 42 patients with Paget's disease and 36 control subjects. Of the PD subjects, 52.4% had arteriosclerotic calcification versus 30.6% of controls (P = 0.05), and 38.6% of PD patients had medial arterial calcification versus 11.1% of controls (P = 0.05). The mean length of calcification was greater in PD patients: 1.93 +/- 2.85 cm versus 0.84 +/- 1.69 cm in controls (P = 0.04). The thickness of calcification was also greater in PD patients: 1.24 +/- 1.30 mm versus 0.56 +/- 0.94 mm (P = 0.01). Patients with Paget's disease more frequently had medial arterial or arteriosclerotic calcification than controls. These calcifications were longer and thicker. Our clinical study therefore confirms that abnormal vessel wall calcification and bone remodeling in Paget's disease are probably linked, although the mechanism of this relation is as yet unexplained.

Teaching in the new NHS: the specialised ward based teacher.

OBJECTIVES: To evaluate the effects of introducing specialised ward based teachers (WBTs) who had a broad remit to improve third year medical undergraduates' clinical experience. DESIGN: Quantitative and qualitative methods including interviews with WBTs, participating consultants and SIFT co-ordinator; student questionnaire and evaluations; analysis of Objective Structured Clinical Examination (OSCE) scores to ascertain if exposure to WBTs affected OSCE scores. SETTING: Two university teaching hospitals. PARTICIPANTS: Third year undergraduate medical students from one school of medicine; four WBTs; 25 consultants; SIFT co-ordinator. MAIN OUTCOME MEASURES: Student evaluations. Student questionnaires. Student OSCE scores. Interview data. RESULTS: WBTs had a demonstrable effect on student performance in OSCE examinations. 94% of students either agreed or strongly agreed that WBTs had helped them develop their examination skills and 87% either agreed or strongly agreed that WBTs had helped them develop their history taking skills. Interview data indicated that the consultants and SIFT co-ordinator considered that WBTs made an important contribution to clinical teaching. CONCLUSIONS: This study suggests that specialised WBTs are one way to manage clinical experience and enhance learning of undergraduate medical students. As clinical teaching moves into earlier parts of the undergraduate curriculum and into the community there is potential for this role to be developed.