Controlled release of biological factors for endogenous progenitor cell migration and intervertebral disc extracellular matrix remodelling.

The recent description of resident stem/progenitor cells in degenerated intervertebral discs (IVDs) supports the notion that their regenerative capacities could be harnessed to stimulate endogenous repair of the nucleus pulposus (NP). In this study, we developed a delivery system based on pullulan microbeads (PMBs) for sequential release of the chemokine CCL-5 to recruit these disc stem/progenitor cells to the NP tissue, followed by the release of the growth factors TGF-ß1 and GDF-5 to induce the synthesis of a collagen type II- and aggrecan-rich extracellular matrix (ECM). Bioactivity of released CCL5 on human adipose-derived stem cells (hASCs), selected to mimic disc stem/progenitors, was demonstrated using a Transwell® chemotaxis assay. The regenerative effects of loaded PMBs were investigated in ex vivo spontaneously degenerated ovine IVDs. Fluorescent hASCs were seeded on the top cartilaginous endplates (CEPs); the degenerated NPs were injected with PMBs loaded with CCL5, TGF-ß1, and GDF-5; and the IVDs were then cultured for 3, 7, and 28 days to allow for cell migration and disc regeneration. The PMBs exhibited sustained release of biological factors for 21 days. Ex vivo migration of seeded hASCs from the CEP toward the NP was demonstrated, with the cells migrating a significantly greater distance when loaded PMBs were injected (5.8 ± 1.3 mm vs. 3.5 ± 1.8 mm with no injection of PMBs). In ovine IVDs, the overall NP cellularity, the collagen type II and the aggrecan staining intensities, and the Tie2+ progenitor cell density in the NP were increased at day 28 compared to the control groups. Considered together, PMBs loaded with CCL5/TGF-ß1/GDF-5 constitute an innovative and promising strategy for controlled release of growth factors to promote cell recruitment and extracellular matrix remodelling.

In vitro and in vivo evaluation of an electrospun-aligned microfibrous implant for Annulus fibrosus repair.

Annulus fibrosus (AF) impairment is associated with reherniation, discogenic pain, and disc degeneration after surgical partial discectomy. Due to a limited intrinsic healing capacity, defects in the AF persist over time and it is hence necessary to adopt an appropriate strategy to close and repair the damaged AF. In this study, a cell-free biodegradable scaffold made of polycaprolactone (PCL), electrospun, aligned microfibers exhibited high levels of cell colonization, alignment, and AF-like extracellular matrix deposition when evaluated in an explant culture model. The biomimetic multilayer fibrous scaffold was then assessed in an ovine model of AF impairment. After 4 weeks, no dislocation of the implants was detected, and only one sample out of six showed a partial delamination. Histological and immunohistochemical analyses revealed integration of the implant with the surrounding tissue as well as homogeneously aligned collagen fiber organization within each lamella compared to the disorganized and scarcer fibrous tissue in a randomly organized control fibrous scaffold. In conclusion, this biomimetic electrospun implant exhibited promising properties in terms of AF defect closure, with AF-like neotissue formation that fully integrated with the surrounding ovine tissue.

Long-Term Follow-Up Comparative Study of Hydroxyapatite and Autologous Cranioplasties: Complications, Cosmetic Results, Osseointegration.

OBJECTIVE: A three-dimensional reconstruction technique using the CustomBone (CB) prosthesis allows custom-made cranioplasty (CP) possessing osseointegration properties owing to its porous hydroxyapatite (HA) composition. This reconstruction technique has replaced less expensive techniques such as subcutaneously preserved autologous bone (SP). Our primary objective was to evaluate complications between CB and SP CP techniques. A secondary objective was to assess cosmetic results and osseointegration of CPs. METHODS: This single-center study comprised patients undergoing delayed CB or SP CP after craniectomy between 2007 and 2014. A prospective interview was conducted to collect all data, including 2-year follow-up clinical and radiologic data. Cosmetic results were assessed by a qualitative score, and osseointegration was assessed by measuring relative fusion at the CP margins. RESULTS: Of 100 patients undergoing CB or SP CP between 2007 and 2014, 92 (CB, n = 44; SP, n = 48) participated in the prospective interview. No significant difference in complication rates was observed between the 2 groups. The main complication specific to the CB group was fracture of the prosthesis observed in 20.8% patients. A higher rate of good cosmetic results was observed in the CB group (92.5% vs. 74.3%, P = 0.031). In the CB group, 51% of patients demonstrated no signs of bone fusion of the CP. CONCLUSIONS: Although the CB prosthesis is associated with cosmetic advantages, the porous hydroxyapatite composition makes it fragile in the short-term and long-term, and effective osseointegration remains uncertain.

Non neurologic burst thoracolumbar fractures fixation: Case-control study.

STUDY DESIGN: Burst fractures not associated with any neurological deficits are frequent but not therapeutic agreement on their management is available to date. This case-control study was conducted to try to help guide therapeutic decision in the treatment of such fractures. MATERIALS AND METHODS: This case-control study includes consecutive retrospective evaluation of 25 case-patients treated by posterior short-segment fixation associated with kyphoplasty (SFK) in the treatment of A3 thoracolumbar unstable fractures, as compared to a control-group composed of 82 patients treated by long-segment (LF) pedicle screws. RESULTS: SFK patients bled significantly less than the LF patients (p=0.04). Assessment of deformation progression, vertebral height restoration and reduction of the regional kyphotic angle in the SFK and LF groups revealed no statistically significant superiority of one approach on another. In contrast, the height of endplates was significantly increased in the SFK group (p=0.006). The patients' pain levels were significantly improved in the SFK group (p=0.002). However, patients from the SFK group stood earlier postoperatively (1.7 vs 3.7days, p=0.001). CONCLUSION: We believe that SFK in vertebral fractures is as efficient as LF for bone consolidation and spine stabilization. In addition, SFK patients may use fewer analgesics.

Natural course and prognosis of anaplastic gangliogliomas: a multicenter retrospective study of 43 cases from the French Brain Tumor Database.

Background: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. Methods: Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively. Results: Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis. Conclusions: We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival.

Overall Survival in Spine Myeloma Metastases: Difficulties in Predicting With Prognostic Scores.

STUDY DESIGN: Fifty-one patients with spinal multiple myeloma (MM) metastases were operated and followed between January 2004 and July 2014. OBJECTIVE: The aim of this study was to consider the efficiency of surgical prognosis scores in the management of spinal metastases myelomas. SUMMARY OF BACKGROUND DATA: The spine is the most common site of bone metastases in MM. Surgery in spine metastases MM is a matter of debate and its impact on the increase of a patient's survival time is not clear. Several surgical survival scores have been developed to determine the best treatment in these patients. METHODS: We studied 51 patients operated for spinal MM metastases between January 2004 and July 2014. We determined the Tokuhashi and Tomita survival scores and compared them with documented patient survivals. The two scores were also compared with the International Staging System (ISS). RESULTS: Median survival (MS) was 108 months [standard deviation (SD) 62] for ISS I, 132.2 (SD 40) for ISS II, and 45.5 months (SD 16.3) for ISS III (P = 0.09). According to Tokuhashi survival score, 21 patients (41.2%) will survive <6 months, 6 (11.8%) 6 to 12 months, and 24 (47%) >12 months. According to Tomita et al., 50 patients (98%) will survive >49.9 months and 1 patient (2%) <15 months. Regardless of the ISS grade prognosis, Tokuhashi survival score, and to a lesser extent Tomita score, underestimated the actual survival very significantly [P < 0.0001, Log Rank (Mantel-Cox)]. CONCLUSION: We suggest that spine surgical prognosis scores are not accurate and are not able to predict the survival of patients with spine myeloma metastases. Spine surgeons have to be guided not by the initial ISS stage but rather by spinal instability and neurological status. LEVEL OF EVIDENCE: N/A.

Predictors of survival in patients with surgical spine multiple myeloma metastases.

BACKGROUND: Multiple myeloma (MM) is the most common primary malignant tumor of the spine and bone. Spinal metastases are part of the evolution and progression of the MM disease. Therefore, this study aims at investigating prognostic factors associated with overall survival (OS) in patients with symptomatic spine MM metastases. METHODS: Consecutive spine surgery procedures were performed in the largest series reported to date and comprising 51 patients with osteolytic vertebral compression fractures resulting from MM, diagnosed by either bone marrow or tumor biopsy. RESULTS: The mean age of patients was 61.1 years and mean follow-up was 31.9 months. Through univariate analyses, ISS stage (p < 0.0001), preoperative spine instability (SINS score) (p < 0.03), posterior osteosynthesis fixation (p < 0.002), preoperative adjuvant therapy (p < 0.02), postoperative adjuvant treatment (p < 0.001), bone marrow transplant (p < 0.03) and newly MM diagnosed (p < 0.03) emerged as powerful predictors of survival. Cox multivariate proportional hazard model indicated that only ISS Stage and stabilization surgery such as osteosynthesis were two independent predictive factors for OS [hazard ratio (HR): 0.268, 95% confidence interval (CI) 0.07-0.536; p < 0.006 for the former and HR: 0.184, 95% confidence interval (CI) 0.03-0.89; p < 0.04 for the latter]. CONCLUSION: Stabilization surgery combined to ISS staging should be considered as an important prognostic survival factor for patients with symptomatic MM spine metastases.

Odontoid balloon kyphoplasty associated with screw fixation for Type II fracture in 2 elderly patients.

Anterior screw fixation is a well-recognized technique that is used to stabilize Type IIB fractures of the odontoid process in the elderly. However, advanced age and osteoporosis are 2 risk factors for pseudarthrosis. Kyphoplasty has been described in the treatment of lytic lesions in C-2. The authors decided to combine these 2 techniques in the treatment of unstable fractures of the odontoid. Two approximately 90-year-old patients were treated for this type of fracture. Instability was demonstrated on dynamic radiography in one patient, and the fracture was seen on static radiography in the other. Clinical parameters, pain, range of motion, 36-Item Short Form Health Survey (SF-36) score (for the first patient), and radiological examinations (CT scans and dynamic radiographs) were studied both before and after surgery. After inflating the balloon both above and below the fracture line, the authors applied a high-viscosity polymethylmethacrylate cement. Some minor leakage of cement was noted in both cases but proved to be harmless. The screws were correctly positioned. The clinical result was excellent, both in terms of pain relief and in the fact that there was no reduction in the SF-36 score. The range of motion remained the same. A follow-up CT scan obtained 1 year later in one of the patients showed no evidence of change in the materials used, and the dynamic radiographs showed no instability. This combination of kyphoplasty and anterior screw fixation of the odontoid seems to be an interesting technique in osteoporotic Type IIB fractures of the odontoid process in the elderly, with good results both clinically and radiologically.

A cost-minimization analysis in minimally invasive spine surgery using a national cost scale method.

INTRODUCTION: The last decade has seen the emergence of minimally invasive spine surgery. However, there is still no consensus on whether percutaneous osteosynthesis (PO) or open surgery (OS) is more cost-effective in treatment of traumatic fractures and degenerative lesions. The objective of this study is to compare the clinical results and hospitalization costs of OS and PO for degenerative lesions and thoraco-lumbar fractures. METHODS: This cost-minimization study was performed in patients undergoing OS or PO on a 36-month period. Patient data, surgical and clinical results, as well as cost data were collected and analyzed. The financial costs were calculated based on diagnosis related group reimbursement and the French national cost scale, enabling the evaluation of charges for each hospital stay. RESULTS: 46 patients were included in this cost analysis, 24 patients underwent OS and 22 underwent PO. No significant difference was found between surgical groups in terms of patient's clinical features and outcomes during the patient hospitalization. The use of PO was significantly associated with a decrease in Length Of Stay (LOS). The cost-minimization revealed that PO is associated with decreased hospital charges and shorten LOS for patients, with similar clinical outcomes and medical device cost to OS. CONCLUSIONS: This medico-economic study has leaded to choose preferentially the use of minimally invasive surgery techniques. This study also illustrates the discrepancy between the national health system reimbursement and real hospital charges. The medico-economic is becoming critical in the current context of sustainable health resource allocation.

Study of the long-term results of decompressive craniectomy after severe traumatic brain injury based on a series of 60 consecutive cases.

BACKGROUND: Decompressive craniectomy can be proposed in the management of severe traumatic brain injury. Current studies report mixed results, preventing any clear conclusions on the place of decompressive craniectomy in traumatology. METHODS: The objective of this retrospective study was to evaluate the results of all decompressive craniectomies performed between 2005 and 2011 for refractory intracranial hypertension after severe traumatic brain injury. Sixty patients were included. Clinical parameters (Glasgow scale, pupillary examination) and radiological findings (Marshall CT scale) were analysed. Complications, clinical outcome, and early and long-term Glasgow Outcome Scale (GOS) were evaluated after surgery. Finally, the predictive value of preoperative parameters to guide the clinician's decision to perform craniectomy was studied. RESULTS: Craniectomy was unilateral in 58 cases and the mean bone flap area was 100 cm(2). Surgical complications were observed in 6.7% of cases. Mean followup was 30 months and a favourable outcome was obtained in 50% of cases. The initial Glasgow Scale was the only statistically significant predictive factor for long-term outcome. CONCLUSION: Despite the discordant results in the literature, this study demonstrates that decompressive craniectomy is useful for the management of refractory intracranial hypertension after severe traumatic brain injury.

Symptomatic vertebral hemangiomas during pregnancy.

Symptomatic vertebral hemangiomas during pregnancy are rare, as only 27 cases have been reported in the literature since 1948. However, symptomatic vertebral hemangiomas can be responsible for spinal cord compression, in which case they constitute a medical emergency, which raises management difficulties in the context of pregnancy. Pregnancy is a known factor responsible for deterioration of these vascular tumors. In this paper, the authors report 2 clinical cases of symptomatic vertebral hemangiomas during pregnancy, including 1 case of spontaneous fracture that has never been previously reported in the literature. The authors then present a brief review of the literature to discuss emergency management of this condition. The first case was a 28-year-old woman at 35 weeks of gestation, who presented with paraparesis. Spinal cord MRI demonstrated a vertebral hemangioma invading the body and posterior arch of T-3 with posterior epidural extension. Laminectomy and vertebroplasty were performed after cesarean section, allowing neurological recovery. The second case involved a 35-year-old woman who presented with spontaneous fracture of T-7 at 36 weeks of gestation, revealing a vertebral hemangioma with no neurological deficit, but it was responsible for pain and local instability. Treatment consisted of postpartum posterior interbody fusion. With a clinical and radiological follow-up of 2 years, no complications and no modification of the hemangiomas were observed. A review of the literature reveals discordant management of these rare cases, which is why the treatment course must be decided by a multidisciplinary team as a function of fetal gestational age and maternal neurological features.

A case of atypical chronic subdural hematoma: a spontaneous rupture of dural lymphoma nodule.

In forensic medicine, a chronic subdural hematoma (SDH) usually results from trauma, sometimes minimal for elderly people. The case reported here is a forensic medical description of an atypical chronic subdural hematoma. A woman aged of 40-year-old died following a coma. The autopsy and histological analyses revealed the hemorrhagic disintegration of a lymphoid nodule, a metastasis from generalized lymphoma. The combination of chronic symptomatic SDH and a tumor of the dura mater have been described, but are very rare. The possibility of trauma, even minimal, has never been excluded in these cases. In fact, the clinical picture of these patients suggested a significant movement of the brain within the cranial cavity due to the physiological decrease in brain volume. In the reported case, this particular process was excluded since the spontaneous hemorrhagic effusion produced by the meningeal lymphoid nodule was the cause of the chronic SDH. This pathophysiological explanation was possible because the entire brain and meninges were removed for histological analysis. Trauma, even minimal trauma, is not always involved in the formation of a chronic SDH.

Laser-treated Nucleus pulposus as an innovative model of intervertebral disc degeneration.

This study describes an innovative experimentally induced model of intervertebral disc degeneration. This innovative approach is based on the induction of extracellular matrix disorders in the intervertebral disc (IVD) using a diode laser. For this study, 15 one-year-old and five 30-month-old New Zealand White rabbits were used. Two procedures were tested to trigger IVD degeneration: needle aspiration (reference technique) and a laser approach. The IVD degeneration process was assessed 20, 40, 60, 90 and 120 days after surgery by X-ray radiography (IVD height), magnetic resonance imaging (MRI) (T2 intensity of IVD signal) and histological analysis using modified Boos' scoring. Our data indicate that a marked IVD degeneration was found compared with sham-operated animals regardless of the procedure tested. A significant decrease in disc height on X-ray radiographs was first demonstrated. In addition, MRI disc signals were significantly reduced in both groups. Finally, a statistically significant increase in Boos' scoring was found in both laser and aspiration-induced IVD degeneration. Interestingly, IVD degeneration induced by laser treatment was more progressive compared with aspiration. Moreover, the histological results indicated that laser-induced disc degeneration was quite similar to that obtained during the natural aging process as observed in 30-month-old rabbits. Our study describes the consistency of this innovative experimentally-induced animal model of IVD degeneration. The radiological, MRI and histological data confirm its relevance. The histological examination indicates that IVD degeneration induced by laser treatment is comparable to the degenerative process observed during the onset of spontaneous IVD degeneration. This model could be a useful tool to help us validate biomaterial-assisted, cell-based, regenerative medicine strategies for the prevention and treatment of IVD degeneration.

Epidemiological surveillance of lumbar disc surgery in the general population: a pilot study in a French region.

OBJECTIVES: Disc-related sciatica (DRS) is a significant and costly health problem in the working population. The aim of this pilot study was to assess the feasibility of a surveillance system for DRS using hospital databases for lumbar disc surgery (LDS). METHODS: A total of 272 inpatients (119 men and 153 women) living in a French region and discharged in 2002-2003 from a spine center of a large University Hospital following LDS were compared with demographic and socioeconomic data on the population of the same region. Medical and occupational histories were gathered using a mailed questionnaire. The age-adjusted relative risks and population attributable fraction of risk (PAF) were calculated in relation to occupations and industries. RESULTS: Information on employment was available for the 75 women and 71 men. The risk of LDS varied according to occupations and industries. PAFs ranged between 30% (12-48) for male blue collar workers and 22% (4-40) for female lower white collar workers. PAFs ranged between 7 and 17% in the economic sectors at high risk. CONCLUSION: The surveillance of LDS can identify occupations and industries at risk.

Identification of phenotypic discriminating markers for intervertebral disc cells and articular chondrocytes.

OBJECTIVE: The present study was conducted to improve our knowledge of intervertebral disc (IVD) cell biology by comparing the phenotype of nucleus pulposus (NP) and annulus fibrosus (AF) cells with that of articular chondrocytes (ACs). METHODS: Rabbit cells from NP and AF were isolated and their phenotype was compared with that of AC by real-time PCR analysis of type I (COL1A1), II (COL2A1) and V (COL5A1) collagens, aggrecan transcript (AGC1), matrix Gla protein (MGP) and Htra serine peptidase 1 (Htra1). RESULTS: Transcript analysis indicated that despite certain similarities, IVD cells exhibit distinct COL2A1/COL1A1 and COL2A1/AGC1 ratios as compared with AC. The expression pattern of COL5A1, MGP and Htra1 makes it possible to define a phenotypic signature for NP and AF cells. CONCLUSIONS: Our study shows that NP and AF cells exhibit a clearly distinguishable phenotype from that of AC. Type V collagen, MGP and HtrA1 could greatly help to discriminate among NP, AF and AC cells.

Arachnoiditis ossificans of the cauda equina. Case report and review of the literature.

The authors describe a case of arachnoiditis ossificans (AO) of the cauda equina. The lesion is a rare pathological entity usually confined to the thoracic and high lumbar regions that can cause progressive spinal cord and cauda equina compression, inducing severe neurological deterioration. The authors analyze the clinical symptoms, radiological features, histological data, and treatment options relating to this case and 13 others described in the literature; additionally, they consider the possible mechanisms responsible for ossification of the leptomeninges. Although clustered arachnoidal cells are usually implicated in its pathogenesis, an environment induced by arachnoiditis and disturbed cerebrospinal fluid flow appears to be a more important factor. A therapeutic strategy is proposed for AO for which no effective treatment currently exists.

Inverted-hook occipital clamp system in occipitocervical fixation. Technical note.

The authors describe an occipitocervical fixation procedure in which they use inverted occipital hooks inserted through a burr hole drilled in the squamous part of the occipital bone. Fifteen patients with unstable lesions of the occipitocervical junction underwent occipitocervical internal fixation. The mean follow-up period was 21 months (range 2-63 months). No implant failed, and postoperative immobilization was not required. The placement of a posterior occipitocervical graft (for which fusion is uncertain) can be avoided in certain conditions.