Multivariate Analysis of RNA Chemistry Marks Uncovers Epitranscriptomics-Based Biomarker Signature for Adult Diffuse Glioma Diagnostics.

One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of "biomarker signatures" that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an "epitranscriptomics-based signature" that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.

[Choice optimisation of radiation therapy technique for central neurocytomas from literature data]. / Optimisation du choix de la technique d'irradiation des neurocytomes centraux à partir des données de la littérature.

Neurocytomas represent 0,25 to 0,5 of brain tumours. These tumours have neuronal differentiation. It's a young adult disease. The main treatment is neurosurgery. The place of other therapies is still unclear, noticeably with regards to radiotherapy. This review aim is to determine the place and the modalities of radiotherapy in the management of neurocytomas. A literature search using PubMed allowed to select the most relevant studies. Finally, 22 studies were selected according to pre-established criteria to answer the problem. All studies were retrospective studies except one. The analysis conclusion defined radiotherapy as a treatment of choice in selected patients, when surgical resection was incomplete or when tumour was atypical.

Transformation Foci in IDH1-mutated Gliomas Show STAT3 Phosphorylation and Downregulate the Metabolic Enzyme ETNPPL, a Negative Regulator of Glioma Growth.

IDH1-mutated gliomas are slow-growing brain tumours which progress into high-grade gliomas. The early molecular events causing this progression are ill-defined. Previous studies revealed that 20% of these tumours already have transformation foci. These foci offer opportunities to better understand malignant progression. We used immunohistochemistry and high throughput RNA profiling to characterize foci cells. These have higher pSTAT3 staining revealing activation of JAK/STAT signaling. They downregulate RNAs involved in Wnt signaling (DAAM2, SFRP2), EGFR signaling (MLC1), cytoskeleton and cell-cell communication (EZR, GJA1). In addition, foci cells show reduced levels of RNA coding for Ethanolamine-Phosphate Phospho-Lyase (ETNPPL/AGXT2L1), a lipid metabolism enzyme. ETNPPL is involved in the catabolism of phosphoethanolamine implicated in membrane synthesis. We detected ETNPPL protein in glioma cells as well as in astrocytes in the human brain. Its nuclear localization suggests additional roles for this enzyme. ETNPPL expression is inversely correlated to glioma grade and we found no ETNPPL protein in glioblastomas. Overexpression of ETNPPL reduces the growth of glioma stem cells indicating that this enzyme opposes gliomagenesis. Collectively, these results suggest that a combined alteration in membrane lipid metabolism and STAT3 pathway promotes IDH1-mutated glioma malignant progression.

WHO grade II meningioma: Epidemiology, survival and contribution of postoperative radiotherapy in a multicenter cohort of 88 patients.

BACKGROUND: Meningioma is the most common primary intracranial tumor, representing 13-36.6% of all primary central nervous system tumors. Meningiomas are benign in about 90% of cases. World Health Organization (WHO) grade II meningioma is associated with a high rate of recurrence and poorer survival than in grade I. The reference treatment is surgery, which should be as complete as possible. Currently, in grade II, there are no recommendations for systematic adjuvant treatment such as radiotherapy. We studied a homogeneous series of grade II meningiomas treated by surgery in two university hospital centers to analyze use of radiotherapy and its efficacy. METHODS: We retrospectively analyzed patients in our database with WHO grade II meningioma, operated on between 2007 and 2010 in the university hospitals of Montpellier and Bordeaux, France. Clinical and radiological data, treatments and survival were analyzed. RESULTS: Eighty-eight patients were included. Five-year overall survival was 89.7%. Nineteen patients received radiotherapy during follow-up, without significant impact on survival (P=0.27). CONCLUSION: In WHO grade II meningioma, it is currently difficult to establish clear recommendations for radiotherapy. The present study is in accordance with the literature that early postoperative radiotherapy is not mandatory in grade II meningioma with macroscopically total resection.

Epidemiology of meningiomas.

Although they represent about a third of all the tumors of the central nervous system, knowledge concerning meningioma epidemiology (including incidence data and exploration of the risk factors) remains scarce compared to that of gliomas. A limited number of cancer registries worldwide only record malignant brain tumors, however their completeness and accuracy have been questioned. Even if comparisons are made difficult due to differences in methodologies, available annual incidence rates (sex- and age-standardized, generally on US or World standard population), provided by population-based registries range from 1.3/100,000 to 7.8/100,000 for cerebral meningiomas. An increase in the incidence of primary brain tumors in general and of meningiomas in particular has been observed during the past decades in several countries. It has been suggested that this trend could be artefactual and could be the resultant of an ageing population, improvement in health access and in diagnostic procedures, changes in coding classification for tumors recorded in registries, and/or an increase in the rate of histological confirmation, even in the elderly. All these factors are likely to play a role but they might not fully explain the increase in incidence, observed in most age groups. In addition to intrinsic risk factors (gender, ethnic groups, allergic conditions, familial and personal history, genetic polymorphisms), some exogenous risk factors have been suspected to play a role in the etiology of meningiomas and their changes with time is likely to impact incidence trends. A causal link has been established only for ionising radiation but the role of many other factors have been hypothesised: electromagnetic fields, nutrition, pesticides, hormonal as well as reproductive factors. Considering the serious or even lethal potentiality of some meningiomas and the apparent rise in their incidence, all practitioners involved in neuro-oncology should feel concerned today of the necessity to better assess their public health burden and to study their epidemiological features.

Descriptive epidemiology of 13,038 newly diagnosed and histologically confirmed meningiomas in France: 2006-2010.

PURPOSE: This work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. METHODS: The methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. RESULTS: From 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. DISCUSSION/CONCLUSION: Given the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors.

Cellular and molecular characterization of IDH1-mutated diffuse low grade gliomas reveals tumor heterogeneity and absence of EGFR/PDGFRα activation.

Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment. In oligodendrogliomas, cells express the transcription factors MYT1, Nkx2.2, Olig1, Olig2, Sox8, four receptors (EGFR, PDGFRα, LIFR, PTPRZ1) but not the co-receptor NG2 known to be expressed by oligodendrocyte progenitor cells. A variable fraction of cells also express the more mature oligodendrocytic markers NOGO-A and MAG. DLGG cells are also stained for the young-neuron marker doublecortin (Dcx) which is also observed in oligodendrocytic cells in nontumoral human brain. In astrocytomas, MYT1, PDGFRα, PTPRZ1 were less expressed whereas Sox9 was prominent over Sox8. The phenotype of DLGG cells is overall maintained in culture. Phospho-array screening showed the absence of EGFR and PDGFRα phosphorylation in DLGG but revealed the strong activation of p44/42 MAPK/ERK which was present in a fraction of tumoral cells but also in nontumoral cells. These results provide evidence for the existence of close relationships between the cellular phenotype and the mutations found in DLGG. The slow proliferation of these tumors may be associated with the absence of activation of PDGFRα/EGFR receptors.

[Adult intramedullary gliomas]. / Tumeurs gliales intramédullaires de l'adulte : la série du rapport.

OBJECTIVES: Intramedullary gliomas are rare tumors accounting for less than 4% of all primary central nervous system tumors. The aims of this retrospective multicenter study were to assess their natural outcome as well as management. METHODS AND MATERIALS: We studied 332 patients from 1984 to 2011. Histopathological examination revealed 72% ependymomas (94% were low grade tumors), 24% astrocytomas (29% were high grade tumors), 2.4% mixed gliomas and 1.7% oligodendrogliomas. RESULTS: The mean age at diagnosis was 42.4 years for ependymomas, with male predominance, versus 39.6 years for astrocytomas. Pain was the most common initial presentation. In 20% of cases, astrocytomas were biopsied alone, but more than 80% of ependymomas had surgical resection. Radiotherapy and chemotherapy were reserved for malignant tumors, especially if they were ependymomas. The 5-year survival rate was 76.8% for astrocytomas and 94.5% for ependymomas. Histology, functional status prior to surgery, and tumor grade are among the prognostic factors. CONCLUSION: Our study showed that surgical treatment of gliomas is well codified, at least for ependymomas, but adjuvant treatment continues to play a marginal role in the management even in astrocytomas, which are infiltrative tumors.

TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.

Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAi(Met)-overexpressing cells, PKCα overexpression decreased tRNAi(Met) expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAi(Met) expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.

Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study.

Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.

[Surgery of brain metastases]. / Place de la chirurgie dans la prise en charge des métastases cérébrales.

Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.

Patterns of care and survival of glioblastoma patients: a comparative study between 2004 and 2008 in Lyon, France.

INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined. METHODS: We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger patients (aged<70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(-4), respectively). Elderly patients (aged≥70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004). CONCLUSION: In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.

[Acute traumatic spinal cord injuries: Epidemiology and prospects]. / Les lésions médullaires traumatiques : épidémiologie et perspectives.

OBJECTIVE: Specify the epidemiological data on the acute spinal cord injuries and define a group of patients that could benefit from cellular transplantation therapy designed with the aim of repair and regeneration of damaged spinal cord tissues. MATERIAL AND METHODS: Five years monocentric (Gui-de-Chauliac Hospital, Montpellier, France) retrospective analysis of patients suffering from spinal cord injury (SCI). Spinal cord injured-patients, defined as sensory-motor complete, underwent a clinical evaluation following American Spinal Injury Association (ASIA) and functional type 2 Spinal Cord Independence Measure (SCIM2) scorings as well as radiological evaluation through spinal cord magnetic resonance imaging (MRI). RESULTS: One hundred and fifty-seven medical records were reviewed and we selected and re-examined 20 patients with complete thoracic spinal cord lesion. Clinical and radiological evaluations of these patients demonstrated, in 75 % of the cases, an absence of clinical progression after a mean of 49months. Radiological abnormalities were constantly present in the initial (at the admission to hospital) and control (re-evaluation) MRI and no reliable predictive criteria of prognosis had been found. DISCUSSION/CONCLUSION: We compare our results to the literature and discuss advantages and limits of cellular transplantation strategies for these patients.

[French brain tumor database: general results on 40,000 cases, main current applications and future prospects]. / Recensement national histologique des tumeurs primitives du système nerveux central : résultats généraux sur 40 000 cas, principales applications actuelles et perspectives.

BACKGROUND AND PURPOSE: This work aimed at prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis was available. The objectives were to (i) create a national database and network to perform epidemiological studies, (ii) implement clinical and basic research protocols, and (iii) harmonize the health care of patients affected by PCNST. METHODS: The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase (FBTDB) (Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the Scientific Societies involved in neuro-oncology in France. RESULTS: From 2004 to 2009, 43,929 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%), tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor resections were performed in 78% cases, while biopsies accounted for 22%. Median age at diagnosis, sex, percentage of resections and number of cryopreserved tumors were detailed for each histology, according to the WHO classification. DISCUSSION/CONCLUSION: Many current applications and perspectives for the FBTDB are illustrated in the discussion. To our knowledge, this work is the first database in Europe, dedicated to PCNST, including clinical, surgical and histological data (with also cryopreservation of the specimens), and which may have major epidemiological, clinical and research implications.

Improving the time-machine: estimating date of birth of grade II gliomas.

OBJECTIVES: Here we present a model aiming to provide an estimate of time from tumour genesis, for grade II gliomas. The model is based on a differential equation describing the diffusion-proliferation process. We have applied our model to situations where tumour diameter was shown to increase linearly with time, with characteristic diametric velocity. MATERIALS AND METHODS: We have performed numerical simulations to analyse data, on patients with grade II gliomas and to extract information concerning time of tumour biological onset, as well as radiology and distribution of model parameters. RESULTS AND CONCLUSIONS: We show that the estimate of tumour onset obtained from extrapolation using a constant velocity assumption, always underestimates biological tumour age, and that the correction one should add to this estimate is given roughly by 20/v (year), where v is the diametric velocity of expansion of the tumour (expressed in mm/year). Within the assumptions of the model, we have identified two types of tumour: the first corresponds to very slowly growing tumours that appear during adolescence, and the second type corresponds to slowly growing tumours that appear later, during early adulthood. That all these tumours become detectable around a mean patient age of 30 years could be interesting for formulation of strategies for early detection of tumours.

Anatomical study of serotonergic innervation and 5-HT(1A) receptor in the human spinal cord.

Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. Translation to either pharmacological and/or cellular therapies in humans requires the mapping of the spinal cord 5-HT innervation and its receptors to determine their involvement in specific functions. Here, we have performed a preliminary mapping of serotonergic processes and serotonin-lA (5-HT(1A)) receptors in thoracic and lumbar segments of the human spinal cord. As in rodents and non-human primates, 5-HT profiles in human spinal cord are present in the ventral horn, surrounding motoneurons, and also contact their presumptive dendrites at lumbar level. 5-HT(1A) receptors are present in the same area, but are more densely expressed at lumbar level. 5-HT profiles are also present in the intermediolateral region, where 5-HT(1A) receptors are absent. Finally, we observed numerous serotonergic profiles in the superficial part (equivalent of Rexed lamina II) of the dorsal horn, which also displayed high levels of 5-HT(1A) receptors. These findings pave the way for local specific therapies involving cellular and/or pharmacological tools targeting the serotonergic system.

[Epidemiology of glioblastoma]. / Épidémiologie des glioblastomes.

An increasing incidence of glioblastoma has been observed over the last 30 years. Improvements in diagnostic tools such as CT scans and MRI, changes observed in histological classifications, and adjustments in neurosurgical practices have contributed substantially to this increase. Moreover, the aging of the population and the increasing occurrence of glioblastoma beyond 60 years of age are additional explanations. In Gironde (France), where a specialized registry has been established, the annual incidence of glioblastoma is 4.96/100,000. Wide geographic variations are observed, possibly linked to ethnicity. However, the role of intrinsic and/or extrinsic factors cannot be ruled out. Comparing data between registries is difficult and requires taking into account periods of recruitment and diagnostic tools. Ethnicity, age, sex, hereditary syndromes, some constitutive polymorphisms, and brain irradiation are the established risk factors Allergies or asthma, certain viral infections, autoimmune diseases, nonsteroidal anti-inflammatory drug intake, substitutive hormonal therapy, and dietary antioxidant intake are the established protective factors. Many studies on electromagnetic fields - in particular cellular phones - pesticides, solvents, and other factors have been published. Until now, the results are discordant or are not confirmed because of methodological limitations. Future studies combining constitutive polymorphisms and exposure assessment are likely to provide consistent and important data that will improve our knowledge in the epidemiology of glioblastoma.

[Second surgery for glioblastoma. A 4-year retrospective study conducted in both the Montpellier and Nice Departments of Neurosurgery. A literature review]. / Intérêt d'une seconde chirurgie d'exérèse dans les glioblastomes. Etude rétrospective sur quatre ans aux centres hospitalo-universitaires de Montpellier et de Nice et revue de la littérature.

BACKGROUND AND PURPOSE: Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed. METHODS: We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included. RESULTS: During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months. CONCLUSIONS: The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results.

Strategies for spinal cord repair after injury: a review of the literature and information.

INTRODUCTION: Thanks to the Internet, we can now have access to more information about spinal cord repair. Spinal cord injured (SCI) patients request more information and hospitals offer specific spinal cord repair medical consultations. OBJECTIVE: Provide practical and relevant elements to physicians and other healthcare professionals involved in the care of SCI patients in order to provide adequate answers to their questions. METHOD: Our literature review was based on English and French publications indexed in PubMed and the main Internet websites dedicated to spinal cord repair. RESULTS: A wide array of research possibilities including notions of anatomy, physiology, biology, anatomopathology and spinal cord imaging is available for the global care of the SCI patient. Prevention and repair strategies (regeneration, transplant, stem cells, gene therapy, biomaterials, using sublesional uninjured spinal tissue, electrical stimulation, brain/computer interface, etc.) for the injured spinal cord are under development. It is necessary to detail the studies conducted and define the limits of these new strategies and benchmark them to the realistic medical and rehabilitation care available to these patients. CONCLUSION: Research is quickly progressing and clinical trials will be developed in the near future. They will have to answer to strict methodological and ethical guidelines. They will first be designed for a small number of patients. The results will probably be fragmented and progress will be made through different successive steps.

Metastatic paraplegia: care management characteristics within a rehabilitation center.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the potential impact of rehabilitation care on associated symptoms and functional improvements of paraplegic patients with metastatic spinal cord compression. SETTING: CMN Propara, Montpellier (France). MEASURES: Demographics, Functional Independence Measure (FIM), Frankel Modified Score and Visual Analog Scale (VAS) for pain, intercurrent adverse medical events and neurological outcome, duration of stay, survival time, rehospitalization in a non-Spinal Cord Injury unit, number of contracts defining the patients rehabilitation goals, number of contracts defining the patients duration of stay within the rehabilitation center. RESULTS: We reviewed the charts of 26 patients. The initial neurological profile was paraplegia or paraparesis for 24 patients and quadriparesis for 2 patients. Regarding functional improvements: four patients demonstrated a poor functional evolution, five patients showed no functional improvements or very slight improvements and all the other patients showed an increase in their overall functional aptitudes. At the end of the stay, 14 patients were urinary independent. Our study reports 52 rehospitalizations in an another unit and 101 outpatient visits during their rehabilitation stay in a physical medicine and rehabilitation (PM&R) center. For the 14 patients who were deceased at the time of data collection, the median survival rate post-paraplegia was 12.7 months. A total of 12 of the 14 patients spent more than a third of their remaining survival time in a rehabilitation center. DISCUSSION: Compared to the patients' life expectancy, their stay in a rehabilitation center is too long and prevents them from spending time with family and loved ones. The occurrence rate of the associated symptoms is high because of both cancer-related disorders and neurological disorders caused by the spinal cord lesion. PM&R professionals are faced with patients affected by chronic pain and fatigue as well as frequent rehospitalizations, short stays and outpatient stays, in the primary oncology unit. This study focuses on the need to privilege the patients' comfort over their functional rehabilitation.