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In 2014, a phase II randomised, double blind clinical trial assessing the efficacy of cholecalciferol (vitamin D3) in patients with a cervical trauma will be set up. This trial stems from previous studies showing that vitamin D supplementation improves functional recovery in rat models of peripheral or central nerve injury. In a first series of experiments, we used a rat model of peripheral nerve trauma to demonstrate the therapeutic efficiency of vitamin D. We first demonstrated that ergocalciferol (vitamin D2) increases the number and the diameter of newly formed axons and improves the response of metabosensitive fibers from tibialis muscle, in a model of transected peroneal nerve. Then, we compared vitamin D2 and vitamin D3 and observed that the latter is more efficient. At the dose of 500 IU/kg/day, vitamin D3 induces a dramatic functional recovery. We also demonstrated that vitamin D3 increases the number of preserved or newly formed axons in the proximal end, the mean axon diameter in the distal end, neurite myelination in both the distal and proximal ends as well as the expression of genes involved in axogenesis and myelination. In parallel, we assessed the therapeutic role of vitamin D on the central nervous system. In a first study, using a rat model of spinal cord compression at the T10 thoracic level, we delivered vitamin D3 (cholecalciferol) orally at the dose of 50 IU/kg/day or 200 IU/kg/day. When compared to control animals, vitamin D-treated rats displayed, three months after injury, a significant improvement of ventilatory frequency and a reduction of H reflex indicating functional improvements at three months post-injury. In a second study, we used a rat model of cervical hemisection (C2) with a higher dose of oral vitamin D3 (500 IU/kg/day) delivered weekly, during 12 weeks. We observed an improved locomotor recovery, a reduced spasticity and a significantly higher rate of axons crossing the lesion site in treated animals. However, it must be pointed out that the functional improvement is reduced when vitamin D is provided one week after the trauma., (© Société de Biologie, 2014.)

Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or spinal cord repair.

The authors report their experience about more than 50 patients with soft tissue defects in the area of the lower leg, of the ankle and of the dorsal aspect of the foot and toes, managed with the Extensor digitorum brevis flap. We have most often performed it with a proximal pedicle. Healing was obtained for all case. Infections of malleola have been treated thank to the better delivery of antibiotics. The donor site shows often delayed healing, but in one case, the harvestment area has presented a complete necrosis, which healed with immobilisation of the ankle with external fixator and dressings. At last, we insist on the fast learning of the procedure and the aim to use it in humanitary mission., (Copyright © 2010. Published by Elsevier SAS.)

This article presents a case report of a cranioplasty performed after a post-craniotomy empyema with osteitis. The skull reconstruction was performed using a bioceramic implant and a combined muscular free flap of latissimus dorsi and serratus anterior. This procedure not only provided coverage of a wide skull defect but also allowed the filling of the intracranial dead space. Clinically, we observed an improvement of the patient's preoperative neurological status with a near-complete correction of her right hemiparaesis and phasic disorders. Eight months after the cranioplasty, (1) no recurrence of infection was noticed; (2) no distortion of the skull was noticeable and (3) the patient again experienced a normal social life. Using computed tomography (CT) scan images, we observed a re-expansion of the left cerebral hemisphere without any dead space or extradural collection. The only observable sequelae were a temporoparietal alopecia (10 cm x 4 cm) and a winging of the scapula, induced by the skin graft and the removal of the lower-third of the serratus anterior muscle, respectively. The use of a muscular free flap associated with a customised biomaterial allows a single-stage reconstruction of extensive skull defect (120 cm(2)) in a previously infected area.

Introduction: Internal fixation continues to be the surgical treatment of choice for trochanteric region hip fractures. Intramedullary nailing is the updated version of the Küntscher Y nail and provides stable osteosynthesis of trochanteric hip fractures, classically achieved by closed reduction., Material and Methods: We report on our experience (which started in 2003), using a new fixation device featuring a metaphyseal antegrade nail locked with two cephalic screws and comprising a diaphyseal distal locking. Between April 2003 and September 2006, the first 100 patients who sustained an extracapsular intertrochanteric hip fracture and indicated for internal fixation were prospectively enrolled in this single-center study., Results: Eighty-six patients (mean age 80.3) were reviewed at 6 months (nine had died, three had failure and two were lost to follow-up) and reported a satisfactory functional outcome (mean Merle d'Aubigné score was 16 and mean Harris Hip score was 90). Union was achieved within a mean delay of 3 months (median 102 days 1/2) in a good anatomical position (mean medialization was 1.86 - ranging from -16 to 0mm, and mean shortening was 1.72 mm - ranging from 0 to 24 mm). Functional recovery was satisfactory with a mean Parker score of 7.52. Total operating time was shortened and good fracture stabilization allowed early weight bearing., Discussion: Classically, such intertrochanteric fractures can be managed either with a dynamic screw-plate type fixation or with an intramedullary nailing device locked through a single cephalic screw and finally, in rare cases, with a hip arthroplasty supplemented with some sort of fixation. Most published clinical studies of screw-plate fixations have generally reported satisfactory results except for unstable fractures associated with a calcar area lesion. Screw-nail fixations featuring a single cephalic screw should be used in these latter fracture patterns. We believe this new implant design will significantly enhance the anatomical result and functional outcome of these fractures; all this is expected to bring about an earlier recovery of patient's walking ability., Conclusion: This original intramedullary nailing system provides reliable internal fixation means for intertrochanteric fractures since it combines the advantage of a closed reduction procedure with a more stable biomechanical construct.

Although surgery techniques improved over the years, the clinical results of peripheral nerve repair remain unsatisfactory. In the present study, we compare the results of a collagen nerve guide conduit to the standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves. We assessed behavioral and functional sensori-motor recovery in a rat model of peroneal nerve transection. A 1cm segment of the peroneal nerve innervating the Tibialis anterior muscle was removed and immediately replaced by a new biodegradable nerve guide fabricated from highly purified type I+III collagens derived from porcine skin. Four groups of animals were included: control animals (C, n=12), transected animals grafted with either an autologous nerve graft (Gold Standard; GS, n=12) or a collagen tube filled with an acellular skeletal muscle matrix (Tube-Muscle; TM, n=12) or an empty collagen tube (Collagen-Tube; CT, n=12). We observed that 1) the locomotor recovery pattern, analyzed with kinetic parameters and peroneal functional index, was superior in the GS and CT groups; 2) a muscle contraction was obtained in all groups after stimulation of the proximal nerve but the mechanical muscle properties (twitch and tetanus threshold) parameters indicated a fast to slow fiber transition in all operated groups; 3) the muscular atrophy was greater in animals from TM group; 4) the metabosensitive afferent responses to electrically induced fatigue and to two chemical agents (KCl and lactic acid) was altered in GS, CT and TM groups; 5) the empty collagen tube supported motor axonal regeneration. Altogether, these data indicate that motor axonal regeneration and locomotor recovery can be obtained with the insertion of the collagen tube RevolNerv. Future studies may include engineered conduits that mimic as closely as possible the internal organization of uninjured nerve.

Accumulating evidence indicates that in addition to its immunosuppressant properties, FK506 (tacrolimus), an FDA-approved molecule, promotes nerve regeneration. However, the neuroprotective and neurotrophic effects of this molecule on sensitive fiber regeneration have never been studied. In order to fill this gap in our knowledge, we assessed the therapeutic potential of FK506 in a rat model of peripheral nerve repair. A 1-cm segment of left peroneal nerve was cut out and immediately autografted in an inverted position. After surgery, the animals were treated with FK506 (1.2 mg/kg/d) via an osmotic pump and compared to untreated animals. Recovery of use of the injured leg was assessed weekly for 12 weeks using a walking track apparatus and a camcorder. At the end of this period, motor and metabosensitive responses of the regenerated axons were recorded and histological analysis was performed. We observed that FK506 significantly: (1) increased the diameter of regenerated axons in the distal portion of the graft; (2) improved the responses of sensory neurons to metabolites such as potassium chloride and lactic acid; and (3) induced a fast-to-slow-fiber-type transition of the tibialis anterior muscle. Taken together, these data indicate that FK506 potentiates metabosensitive nerve fiber regeneration. Pharmacological studies of various dosages and concentrations of FK506 are required before recommending this drug for therapeutic treatment of nerve injuries.

Macrodactyly is a rare congenital anomaly defined by an enlargement of all the structures of fingers or toes. Two forms of macrodactyly have been described. One form is static with an enlargement present at birth and growing proportionately to the other digits. The other is progressive with an enlargement beginning in early childhood and growing faster than that of the normal digits. Macrodactyly is responsible of a functional handicap and an aesthetic prejudice. Treatment may be indicated for this reason. Treatment must be individualised and depends on the proportionate size of the enlarged finger, growth rate and the patient's age when first seen. The parents and the child should be advised that multiple procedures may be required and that the result will be somewhat unsatisfactory. Surgical approaches include either reconstructive surgery or amputation. Amputation is indicated at any age for a large, unsightly and stiff digit that interferes with function of the rest of the hand. In feet with involvement of the lesser toes, proximal amputation has the best cosmetic and functional outcome. Epiphyseal arrest, bulk reduction procedures, finger shortening, lateral closing-wedge osteotomies or stripping of the nerves can be performed in the other cases.

Purpose: Management of chronic scapholunate (SL) instability without osteoarthritis remains controversial. In order to recreate an SL interosseous linkage, some surgeons opt for a limited wrist arthrodesis, whereas others use soft tissue stabilization. The purpose of the current study was to review and assess the therapeutic benefit of the modified Brunelli tenodesis that used the flexor carpi radialis tendon to replicate the stabilizing ligaments of the scaphoid., Methods: Between 2001 and 2005, 19 tenodesis procedures have been performed to correct dynamic or static SL instability without osteoarthritis. On average, patients had surgery 15 months after injury. The mean follow-up was 37 months., Results: After surgery, 15 patients had no to mild pain with a mean visual analog scale score of 3 of 10. The average wrist motion was 50 degrees extension, 41 degrees flexion, 24 degrees radial deviation, and 29 degrees ulnar deviation (75%, 73%, 68%, and 86% of the uninvolved wrists, respectively). The grip strength was 78% of the uninvolved wrists. On radiographs, the mean static SL distance was 2.4 mm (2.8 mm before surgery). There was no widening of the SL gap compared to the immediate postoperative gap. The SL angle improved from a mean preoperative value of 61 degrees to 53 degrees immediately after surgery and rose again to 62 degrees at the time of the review. One patient developed a scapholunate advanced collapse wrist stage 2., Conclusions: Ligament reconstruction using tendon grafts gave satisfactory results to correct reducible chronic SL instability without osteoarthritis. This repair technique achieved a relatively pain-free wrist, with acceptable grip strength and normal SL distance but with a loss in the arc of motion and a loss of correction of SL angle., Type of Study/level of Evidence: Therapeutic IV.

To date, the use of autograft tissue remains the "gold standard" technique for repairing transected peripheral nerves. However, the recovery is suboptimal, and neuroactive molecules are required. In the current study, we focused our attention on vitamin D, an FDA-approved molecule whose neuroprotective and neurotrophic actions are increasingly recognized. We assessed the therapeutic potential of ergocalciferol--the plant-derived form of vitamin D, named vitamin D2--in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury.