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.

[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.

[Mechanisms controlling axonal sprouting at the neuromuscular junction]. / Mécanismes contrôlant le bourgeonnement axonal à la jonction neuromusculaire.

This paper explores the specific roles of sprouting stimuli, perisynaptic Schwann cells and neuromuscular activity in axonal sprouting at the neuromuscular junction in partially denervated muscles. As for sprouting stimuli, insulin-like growth factor II which is generated from inactive muscle fibers in partially denervated and paralysed skeletal muscle is described. Likewise, perisynaptic Schwann cells can induce and guide axonal sprouting in partially denervated muscles. Finally, excessive neuromuscular activity significantly reduces bridging of the perisynaptic Schwann cell processes between denervated and innervated endplates and thereby inhibits axonal sprouting in partially denervated muscle. The lack of neuromuscular activity is also harmful in axonal sprouting, probably by impeding calcium influx into the nerve.

[Synapse formation and regeneration]. / Formation et régénération synaptique.

Synapse formation is probably the key process in neural development allowing signal transmission between nerve cells. As an interesting model of synapse maturation, we considered first the neuromuscular junction (NMJ), whose development is particularly dependent on intercellular interactions between the motor nerve and the skeletal muscle. Nerve and muscle have distinct roles in synaptic compartment differentiation. The initial steps of this differentiation and motor endplate formation require several postsynaptic molecular agents including agrin, the tyrosine kinase receptor MuSK and rapsyn. The agrin or motoneuron dependence of this process continues to be debated while the following steps of axonal growth and postsynaptic apparatus maintenance essentially depend on neuronal agrin and a neuron-specific signal dispersing ectopic AChR aggregate remainders, possibly mediated by acetylcholine itself. Neuregulin is essentially involved in Schwann's cell survival and guidance for axonal growth. In this paper, we will discuss the similarities between Central Nervous System (CNS) synaptic formation and Motor innervation. The limited ability of the CNS to create new synapses after nervous system injury will be then discussed with a final consideration of some new strategies elaborated to circumvent the limitations of lesion extension processes.

[Medical and economic reflections on Restore and Itrel neurostimulation systems for neuropathic pain treatment]. / Réflexion sur l'intérêt médicoéconomique des boîtiers de neurostimulation Restore et Itrel dans le traitement des douleurs neuropathiques chroniques.

In 2007, four patients where implanted with the Restore neurostimulation system for intractable chronic leg pain at the Poitiers Hospital. The potential for improving the patients' quality of life and medical-economic concerns motivated this choice for these highly selected patients. In this paper, we propose brief clinical case reports and discuss the reasons for choosing this new rechargeable system, even though it was initially more expensive than the standard neurostimulation system (Itrel 3). All patients receiving implants declared that they were very satisfied with the quality of stimulation provided by Restore and noted a significant improvement in their quality of life. If this solution becomes advantageous from an economic point of view, clinical data should lend support to the utility of this technological innovation for patients who have hitherto been in treatment failure.

The Na, K-ATPase alpha3-isoform specifically localizes in the Schmidt-Lanterman incisures of human nerve.

INTRODUCTION: To our knowledge, there is little reference in literature with regards to alpha3-isoform of Na+,K+-ATPase in human peripheral nerves. The aim of this study was to determine the expression of the neuronal alpha3-isoform of Na+,K+-ATPase in human sural nerves from patients with a permanent medullary central nervous system injury. MATERIALS AND METHODS: We studied the immunolocalization of alpha3-isoform of Na+,K+-ATPase using a polyclonal antibody against the amino sequence near the phosphorylation site of the alpha3-isoforms of Na+,K+-ATPase using immunohistochemistry and confocal laser scanning microscopy. An antibody specific for alpha2-isoform of Na+,K+-ATPase was used to label the Schwann cells. RESULTS: Morphometric analysis of longitudinal section of human sural nerves showed that the alpha3-isoform of Na+,K+-ATPase was distributed along the length of axolemma. The myelin sheath of the Schwann cells showed clearly a distribution of alpha3- but not alpha2-isoforms of Na+,K+-ATPase at the level of Schmidt-Lanterman incisures. CONCLUSION: The human sural nerve shows a specific localization of the Na+,K+-ATPase alpha3-isoform in the Schmidt-Lanterman incisures of Schwann cells in addition to its localization in axonal membranes.