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.

[Botulinum toxin and painful peripheral neuropathies: what should be expected?]. / Toxine botulique et douleur des neuropathies périphériques : que peut-on en attendre ?

Botulinum toxin type A (BTX-A) is a potent neurotoxin that blocks acetylcholine release from presynaptic nerve terminals by cleaving the SNARE complex. BTX-A has been reported to have analgesic effects independent of its action on muscle tone. The most robust results have been observed in patients with neuropathic pain. Neuropathic pain due to peripheral lesions has been the most widely studied. BTX-A has shown its efficacy on pain and allodynia in various animal models of inflammatory neuropathic pain. The only randomized, double-blind, placebo-controlled trial in patients with focal painful neuropathies due to nerve trauma or postherpetic neuralgia demonstrated significant effects on average pain intensity from 2 weeks after the injections to 14 weeks. Most patients reported pain during the injections, but there were no further local or systemic side effects. The efficacy of BTX-A in painful peripheral neuropathies has been more recently studied. Results were positive in the only study in an animal model of peripheral neuropathy. One study in patients with diabetic painful peripheral neuropathy demonstrated a significant decrease in Visual Analog Scale. In conclusion, one session of multiple intradermal injection of BTX-A produces long-lasting analgesic effects in patients with focal painful neuropathies and diabetic neuropathic pain, and is particularly well tolerated. The findings are consistent with a reduction of peripheral sensitisation, the place of a possible central effect remaining to define. Further studies are needed to assess some important issues, i.e. BTX-A efficacy in patients with small fiber neuropathies and the relevance of early and repeated injections. Future studies could also provide valuable insights into pathophysiology of neuropathic pain.

Intraoperative use of the Medtronic O-arm for deep brain stimulation procedures.

The purpose of this study was to analyze the feasibility and utility of 3D imaging to help lead positioning during a deep brain stimulation (DBS) procedure. A bilateral subthalamic DBS procedure was conducted in 2 patients for idiopathic Parkinson's disease. Subthalamic nucleus targeting was based on preoperative stereotactic MRI. We used the Medtronic O-arm to perform 2D-imaging control (frontal and lateral) as well as quick (<30 s) 3D acquisition. This allowed us to check the positioning of micro-macro electrodes and definite electrodes. 3D images were fused with postoperative CT to assess their accuracy, and with preoperative MRI to visualize the anatomical location of the electrodes. 3D imaging is a quick and safe method to ensure perioperative control of lead placement during DBS procedures.

Using translational medicine to understand clinical differences between botulinum toxin formulations.

When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia.

OBJECTIVES: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia. Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies. The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport. METHODS: A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed. The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four). The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed. RESULTS: Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox. The number of adverse events was higher with both Dysport treatments. The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients. No adverse event required withdrawal of therapy or specific management. CONCLUSIONS: Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects. This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia.

Central nervous system disease in patients with macrophagic myofasciitis.

Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar signs (four out of seven), visual loss (two out of seven), cognitive and behavioural disorders (one out of seven) and bladder dysfunction (one out of seven). Brain T(2)-weighted MRI showed single (two out of seven) or multiple (four out of seven) supratentorial white matter hyperintense signals and corpus callosum atrophy (one out of seven). Evoked potentials were abnormal in four out of six patients and CSF in four out of seven. According to Poser's criteria for multiple sclerosis, the diagnosis was clinically definite (five out of seven) or clinically probable multiple sclerosis (two out of seven). Six out of seven patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical accumulations of PAS (periodic acid-Schiff)-positive macrophages, sparse CD8+ T cells and minimal myofibre damage. Aluminium-containing vaccines had been administered 3-78 months (median = 33 months) before muscle biopsy (hepatitis B virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B virus and tetanus toxoid: two out of seven). The association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias.

Patent foramen ovale: is stroke due to paradoxical embolism?

BACKGROUND AND PURPOSE: A patent foramen ovale has been reported to be significantly more frequent in young stroke patients than in matched control subjects, and paradoxical embolism has been suggested as the main mechanism of stroke in this situation. The present study was designed to test this hypothesis. METHODS: Sixty-eight consecutive patients under 55 years of age presenting with an ischemic stroke had an extensive workup, including transesophageal echocardiography with contrast. We compared the prevalence of criteria for the diagnosis of paradoxical embolism in patients with and without a patent foramen ovale. RESULTS: A patent foramen ovale was found in 32 patients (47%). A Valsalva-provoking activity was present at stroke onset in six patients with a patent foramen ovale and in eight patients with no patent foramen ovale (chi 2 = 0.1, nonsignificant). Clinical/radiological features suggestive of an embolic mechanism were not more frequent in patients with a patent foramen ovale. Clinical evidence of deep vein thrombosis was present in one patient with a patent foramen ovale and in none of the others. No occult venous thrombosis was found in a subgroup of patients with a patent foramen ovale and no definite cause for stroke who underwent venography (n = 13). CONCLUSIONS: Our results do not support the hypothesis that paradoxical embolism is the primary mechanism of stroke in patients with a patent foramen ovale.

Meningeal sarcoidosis, pseudo-meningioma, and pachymeningitis of the convexity.

Two cases of meningeal sarcoidosis with unusual and misleading presentations are reported. In the first case, CT scan, angiographic, and MRI findings were indistinguishable from those of meningioma. CSF pleiocytosis may help in diagnosing sarcoid pseudo-meningioma. The second patient had transient focal deficits and pachymeningitis of the convexity. The transient deficits were probably of epileptic origin based on their response to antiepileptic treatment. The diagnosis of neurosarcoidosis was made only after meningeal biopsy, despite thorough investigations.