Patch-based 3D U-Net and transfer learning for longitudinal piglet brain segmentation on MRI.

BACKGROUND AND OBJECTIVES: In order to study neural plasticity in immature brain following early brain lesion, large animal model are needed. Because of its morphological similarities with the human developmental brain, piglet is a suitable but little used one. Its study from Magnetic Resonance Imaging (MRI) requires the development of automatic algorithms for the segmentation of the different structures and tissues. A crucial preliminary step consists in automatically segmenting the brain. METHODS: We propose a fully automatic brain segmentation method applied to piglets by combining a 3D patch-based U-Net and a post-processing pipeline for spatial regularization and elimination of false positives. Our approach also integrates a transfer-learning strategy for managing an automated longitudinal monitoring evaluated for four developmental stages (2, 6, 10 and 18 weeks), facing the issue of MRI changes resulting from the rapid brain development. It is compared to a 2D approach and the Brain Extraction Tool (BET) as well as techniques adapted to other animals (rodents, macaques). The influence of training patches size and distribution is studied as well as the benefits of spatial regularization. RESULTS: Results show that our approach is efficient in terms of average Dice score (0.952) and Hausdorff distance (8.51), outperforming the use of a 2D U-Net (Dice: 0.919, Hausdorff distance: 11.06) and BET (Dice: 0.764, Hausdorff distance: 25.91). The transfer-learning strategy achieves a good performance on older piglets (Dice of 0.934 at 6 weeks, 0.956 at 10 weeks and 0.958 at 18 weeks) compared to a standard training strategy with few data (Dice of 0.636 at 6 weeks, 0.907 at 10 weeks, not calculable at 18 weeks because of too few training piglets). CONCLUSIONS: In conclusion, we provide a method for longitudinal MRI piglet brain segmentation based on 3D U-Net and transfer learning which can be used for future morphometric studies and applied to other animals.

Security and reliability of CUSTOMBONE cranioplasties: A prospective multicentric study.

BACKGROUND: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis. OBJECTIVE: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years. RESULTS: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection. CONCLUSION: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary.

Acute intracranial hypertension management in metastatic brain tumor: A French national survey.

BACKGROUND: Brain metastases occur in 15-30% of cancer patients and their frequency has increased over time. They can cause intracranial hypertension, even in the absence of hydrocephalus. Emergency surgical management of brain metastasis-related intracranial hypertension is not guided by specific recommendations. OBJECTIVE: We aimed to make a French national survey of emergency management of intracranial hypertension without hydrocephalus in the context of cerebral metastasis. METHODS: A national online survey of French neurosurgeons from 16 centers was conducted, consisting of three clinical files, with multiple-choice questions on diagnostic and therapeutic management in different emergency situations. RESULTS: In young patients without any previously known primary cancer, acute intracranial hypertension due to a seemingly metastatic single brain tumor indicated emergency surgery for all those interviewed; 61% aimed at complete resection; brain MRI was mandatory for 74%. When a primary cancer was known, 74% of respondents were more likely to propose surgery if an oncologist confirmed the possibility of adjuvant treatment; 27% were more likely to operate on an emergency basis when resection was scheduled after multi-disciplinary discussion, prior to acute degradation. CONCLUSION: Currently, there is no consensus on the emergency management of intracranial hypertension in metastatic brain tumor patients. In case of previously known primary cancer, a discussion with the oncology team seems necessary, even in emergency. Decision criteria emerge from our literature review, but require analysis in further studies.

Carmustine wafer implantation for high-grade gliomas: Evidence-based safety efficacy and practical recommendations from the Neuro-oncology Club of the French Society of Neurosurgery.

There is a growing body of evidence that carmustine wafer implantation during surgery is an effective therapeutic adjunct to the standard combined radio-chemotherapy regimen using temozolomide in newly diagnosed and recurrent high-grade glioma patient management with a statistically significant survival benefit demonstrated across several randomized clinical trials, as well as prospective and retrospective studies (grade A recommendation). Compelling clinical data also support the safety of carmustine wafer implantation (grade A recommendation) in these patients and suggest that observed adverse events can be avoided in experienced neurosurgeon hands. Furthermore, carmustine wafer implantation does not seem to impact negatively on the quality of life and the completion of adjuvant oncological treatments (grade C recommendation). Moreover, emerging findings support the potential of high-grade gliomas molecular status, especially the O(6)-Methylguanine-DNA Methyltransferase promoter methylation status, in predicting the efficacy of such a surgical strategy, especially at recurrence (grade B recommendation). Finally, carmustine wafer implantation appears to be cost-effective in high-grade glioma patients when performed by an experienced team and when total or subtotal resection can be achieved. Altogether, these data underline the current need for a new randomized clinical trial to assess the impact of a maximal safe resection with carmustine wafer implantation followed by the standard combined chemoradiation protocol stratified by molecular status in high-grade glioma patients.

[Is the right hemisphere really minor? Involvement in the repair of bodily injury]. / L'hémisphère droit est-il vraiment mineur ? Implication dans la réparation du dommage corporel.

An appraisal mission regarding the repair of physical injury is based on the classification of the effects of injury and scales. These scales are surprisingly incomplete concerning the symptoms due to a right hemisphere injury. However, these symptoms can cause an important handicap in numerous activities, social, affective and professional. This paper reviews the recent functional anatomic knowledge of the right hemisphere functions, visuo-spatial cognition, intentional process and social cognition. The impacts of this appraisal data, as well as suggestions for new scales, are outlined.

[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.

Early presentation of primary glioblastoma.

BACKGROUND: Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. METHODS: We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. RESULTS: In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. CONCLUSIONS: A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis.

[Differential diagnosis of local tumor recurrence or radionecrosis after stereotactic radiosurgery for treatment of brain metastasis]. / Diagnostic différentiel entre récidive tumorale et radionécrose après radiothérapie stéréotaxique d'une métastase cérébrale.

Magnetic resonance imaging (MRI) is a method of choice for follow-up of irradiated brain metastasis. It is difficult to differentiate local tumour recurrences from radiation induced-changes in case of suspicious contrast enhancement. New advanced MRI techniques (perfusion and spectrometry) and amino acid positron-emission tomography (PET) allow to be more accurate and could avoid a stereotactic biopsy for histological assessment, the only reliable but invasive method. We report the case of a patient who underwent surgery for a single, left frontal brain metastasis of a breast carcinoma, followed by adjuvant stereotactic radiotherapy in the operative bed. Seven months after, she presented a local change in the irradiated area on the perfusion-weighted MRI, for which the differentiation between a local tumour recurrence and radionecrosis was not possible. PET with 2-deoxy-((18)F)-fluoro-D-glucose (FDG) revealed a hypermetabolic lesion. After surgical resection, the histological assessment has mainly recovered radionecrosis with few carcinoma cells. The multimodal MRI has greatly contributed to refine the differential diagnosis between tumour recurrence and radionecrosis, which remains difficult. The FDG PET is helpful, in favour of the diagnosis of local tumour recurrence when a hypermetabolic lesion is found. Others tracers (such as carbon 11 or a fluoride isotope) deserve interest but are not available in all centres. Stereotactic biopsy should be discussed if any doubt remains.

Spontaneous oral extrusion of an acrylic vertebral reconstruction 12 years after a vertebrectomy for a Ewing's sarcoma of the cervical spine: a case report.

INTRODUCTION: Primary Ewing sarcoma of the cervical spine is rare, particularly in children population. The surgical management remains a challenge to associate the best oncological resection and to prevent spinal deformity. The situation is complicated owing to paucity of adapted instrumentation and their possible interactions with the growing bone. CLINICAL PRESENTATION: We described the case of a young 19-year-old woman admitted for an oral extrusion of a bone polymethyl methacrylate (PMMA) allograft 12 years after a C4 circumferential vertebrectomy for primary Ewing's sarcoma. The vertebral anterior reconstruction was slowly repulsed by the growing spine giving way to an autologous bone without kyphosis deformation. CONCLUSION: Bone reconstruction remains a challenge after extensive oncological resection particularly in cervical spine of children. Anterior and posterior instrumentation must be associated. The growing spine is not a good host for PMMA allograft and autograft seems to be preferred for anterior column fusion. In spite of the good oncological results, the authors raise the long-term issue of PMMA for vertebral reconstruction in young patients. With a long follow-up, they showed that posterior rigid fixation might prevent the cervical kyphosis.

Autologous bone flap versus hydroxyapatite prosthesis in first intention in secondary cranioplasty after decompressive craniectomy: a French medico-economical study.

BACKGROUND AND PURPOSE: Decompressive craniectomy is the most common justification for cranioplasty. A medico-economial study based on the effective cost of the hydroxyapatite prosthesis, the percentage of autologous bone graft's loss due to bacterial contamination and the healthcare reimbursment, will allow us to define the best strategy in term of Healthcare economy management for the cranioplasties. A comparison was made between the two groups of patients, autologous bone flap versus custom-made prosthesis in first intention, based on the clinical experience of our department of neurosurgery. RESULTS: No differences was shown between the two groups of patients, in terms of lenght of in-hospital stay and population's characteristics or medical codification. The mean cost of a cranioplasty using the autologous bone graft in first intention was €4045, while the use of hydroxyapatite prosthesis led to a cost of €8000 per cranioplasty. CONCLUSION: In term of Healthcare expenses, autologous bone flap should be used in first intention for cranioplasties, unless the flap is contaminated or in specific indications, when the 3D custom-made hydroxyapatite prosthesis should be privilegied.

[Optic nerve schwannoma]. / Schwannome du nerf optique.

OBJECTIVE: To report the occurrence of an orbital schwannoma probably arising from the optic nerve sheath. PATIENT AND METHOD: Clinical case report. RESULTS: A 65-year-old patient presented with a painless, progressive right proptosis over five years. Magnetic resonance imaging revealed an intraconal mass, radiographically consistent with a cavernous hemangioma. Surgical resection was performed and pathology disclosed a schwannoma affecting the optic nerve. The optic nerve, which does not contain Schwann cells, is exceptionally rarely affected by Schwannomas, which may arise from a few sympathetic nerve fibers or from a few ectopic cells, not normally present within the optic nerve. CONCLUSION: The radiologic appearance of the very rare optic nerve Schwannoma may be confused with a cavernous hemangioma, a more common tumor in this location.

Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1.

Taking advantage from the development of SV30, a new analogue of the pro-apoptotic molecule HA14-1, the aim of this study was to functionally evaluate SV30 and to develop safe nanocarriers for its administration. By using an inversion phase process, 57nm organic solvent-free lipid nanocapsules loaded with SV30 (SV30-LNCs) were formulated. Biological performance of SV30 and SV30-LNCs were evaluated on F98 cells that express Bax and Bcl-2, through survival assays, HPLC, flow cytometry, confocal microscopy and spectral imaging. We observed that SV30 alone or in combination with paclitaxel, etoposide or beam radiation could trigger cell death in a similar fashion to HA14-1. Although partially blocked by Z-VAD-fmk, this effect was coincident to caspase-3 activation. Hence, we established that SV30-LNCs improved SV30 biological activity together with a potentiation of the mitochondrial membrane potential decrease. Interestingly, flow cytometry and confocal analysis indicated that SV30 itself conferred to LNCs improved mitochondrial targeting skills that may present a great interest toward the development of mitochondria targeted nanomedicines.

[Surgical treatment of glioblastomas]. / Traitement chirurgical des glioblastomes.

Although the need for glioblastoma surgery to confirm the histology and decrease the mass effect, and therefore the symptoms, is recognized, the value of total resection remains controversial. In practice, the resected glioblastoma ratio is low. Of 952 glioblastomas treated in France in 2004, 56% were resected and 44% biopsied. An analysis of the literature confirms the importance of resection on survival. Perioperative drugs, surgical techniques, as well as intra- and postoperative imaging are analyzed in view of the literature.

[Local antitumor treatments]. / Traitements antitumoraux locaux.

The idea of intraoperative adjuvant treatment is not new. This review describes only the strategies studied in phase III clinical trials. Among these strategies, only Gliadel® obtained marketing authorization. Some immunotoxins, administered by convection-enhanced delivery, and a gene therapy approach using an adenovirus went through a phase II trial and are currently being studied in a phase III trial. Brachytherapy has never been validated by a clinical trial.

[Glioblastoma incident studies from May 2006 to May 2007 in Angers and Nice, France]. / Études des glioblastomes incidents de mai 2006 à mai 2007, Angers-Nice.

The present work is a retrospective study on glioblastomas treated in the Angers and Nice Hospital Departments of Neurosurgery between 2006 and 2007. This study was conducted 2 years after the audit on incident glioblastoma in France in 2004. New events that may modify the care or survival of glioblastoma have occurred since 2004, justifying the present study. The results show that the Karnowsky Index is more often included in the clinical files and that the rate of complete resection has increased, indicating that neurosurgeons are becoming aware of neuro-oncology. Patients with total resection still have the longest survival (14 months). Surprisingly, less than half the patients having surgery received concomitant radiochemotherapy according to the Stupp protocol. Median overall survival remains at 9 months with intention to treat. For patients treated with concomitant chemoradiotherapy with temozolomide, the median survival is 12 months. For patients having a total resection, the median survival is 14 months, whatever adjuvant treatment is used. Median survival for patients having total resection and chemoradiotherapy with temozolomide is 18 months, with a 23.3% 2-year survival rate, less than the ORTC trial rate.

Local implantation of doxorubicin drug eluting beads in rat glioma.

We evaluated the safety and the efficacy of doxorubicin drug eluting beads "CM-BC1" when used locally in a 9L glioma model. Twenty microlitres of 1mg/ml CM-BC1 (4µg/rat), 10mg/ml CM-BC1 (40µg/rat) or unloaded beads were injected into the brain of 27 rats which was analyzed on day 8, month 3 or month 6. Then, after tumor implantation, rats were treated locally: (1) control group; (2) a group receiving 20µl of unloaded beads, (3) a group "3×6Gy whole-brain irradiation" (WBI), (4) a group receiving 20µl of 1mg/ml CM-BC1 and (5) a group receiving 20µl of 1mg/ml CM-BC1 followed by a WBI. Both the unloaded beads and the lower dose of 1mg/ml CM-BC1 were well tolerated with no early deaths in opposite to 10mg/ml CM-BC1. Medians of survival for the "1mg/ml CM-BC1" group and the combination group are respectively 28.9 and 64.4 days. These results were significant compared to the "unloaded beads" group. The rat's survival was not significantly improved in comparison with the radiotherapy group. This preliminary evidence suggests that 1mg/ml CM-BC1 could be interesting for recurrent high-grade gliomas. Further work is necessary to improve this seducing tool.

Intrathecal baclofen in cerebral palsy. A retrospective study of 25 wheelchair-assisted adults.

OBJECTIVE: To study the efficacy and safety of intrathecal baclofen therapy (ITB) in wheelchair-dependent adults with cerebral palsy. PATIENTS AND METHODS: A retrospective analysis and clinical examination of 25 wheelchair-assisted adults with cerebral palsy receiving ITB initiated between 1999 and 2009 in three different cities in western France. RESULTS: ITB improves spasticity and facilitates wheelchair comfort and nursing care. The therapy has an effect on motor disorders and pain. Eighty percent of the ITB patients were satisfied. Dissatisfaction was related to complications or adverse events and not lack of efficacy. Complications occurred in 32% of the patients and transient interruption of the treatment or surgical removal of the ITB pump was necessary in 16% of cases. DISCUSSION AND CONCLUSION: Wider use of ITB in this indication is likely and should lead to a better understanding of the drug's pharmacological effects on motor disorders and pain. Use of the Goal Attainment Assessment Scale or Caregiver Questionnaire can help us.

[Local chemotherapy of malignant glioma: from syringe injections to nanotechnology]. / Chimiothérapie locale dans les gliomes malins: de l'injection à la seringue aux nanotechnologies.

Many arguments support the development of local therapies for malignant gliomas. Simple injections of antimitotic agents into the surgical cavity has been replaced by more sophisticated systems. Tissues can be infused with complex prolonged-release polymeric or lipidic systems with macroscopic, microscopic and now even nanometric particles. But, as for any drug, the developments of these new agents has been long and only very few reach the stage of the clinic trials.