CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma

Background The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. Methods We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. Results CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. Conclusion Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these result

HyperProbe consortium: innovate tumour neurosurgery with innovative photonic solutions

Recent advancements in imaging technologies (MRI, PET, CT, among others) have significantly improved clinical localisation of lesions of the central nervous system (CNS) before surgery, making possible for neurosurgeons to plan and navigate away from functional brain locations when removing tumours, such as gliomas. However, neuronavigation in the surgical management of brain tumours remains a significant challenge, due to the inability to maintain accurate spatial information of pathological and healthy locations intraoperatively. To answer this challenge, the HyperProbe consortium have been put together, consisting of a team of engineers, physicists, data scientists and neurosurgeons, to develop an innovative, all-optical, intraoperative imaging system based on (i) hyperspectral imaging (HSI) for rapid, multiwavelength spectral acquisition, and (ii) artificial intelligence (AI) for image reconstruction, morpho-chemical characterisation and molecular fingerprint recognition. Our HyperProbe system will (1) map, monitor and quantify biomolecules of interest in cerebral physiology; (2) be handheld, cost-effective and user-friendly; (3) apply AI-based methods for the reconstruction of the hyperspectral images, the analysis of the spatio-spectral data and the development and quantification of novel biomarkers for identification of glioma and differentiation from functional brain tissue. HyperProbe will be validated and optimised with studies in optical phantoms, in vivo against gold standard modalities in neuronavigational imaging, and finally we will provide proof of principle of its performances during routine brain tumour surgery on patients. HyperProbe aims at providing functional and structural information on biomarkers of interest that is currently missing during neuro-oncological interventions

Expression des récepteurs à la somatostatine dans les médulloblastomes et les épendymomes

Nous recherchons l'expression des cinq sous-types de récepteurs à la somatostatine dans une série de médulloblastomes et d'épendymomes. Vingt deux médulloblastomes et vingt huit épendymomes sont étudiés. Les données cliniques et l'évolution sont précisées. Les tumeurs sont caractérisées par une étude en microscopie optique et immunohistochimique. L'expression de l'ARNm des cinq sous-types de récepteurs à la somatostatine est recherchée par RT-PCR et celle de la protéine de sst1, sst2A, sst2B par immunohistochimie sur certains médulloblastomes et épendymomes. L'effet anti-prolifératif de la somatostatine est évalué in vitro par l'incorporation de thymidine tritiée sur une lignée de médulloblastome et sur des cellules tumorales de médulloblastome. Des corrélations entre l'expression des différents transcrits et des données histologiques et cliniques sont recherchées : grade, différenciation cellulaire, âge, métastase, récidive, survie. La fiabilité de la scintigraphie à l'octréotide marqué pour le diagnostic et le suivi est étudiée sur huit médulloblastomes et dix épendymomes. Les résultats sont comparés avec ceux obtenus par l'imagerie par résonance magnétique. Tous les récepteurs sont présents à des niveaux variables dans les différentes tumeurs. Dans les deux types histologiques l'ARNm du sst2 est le plus exprimé. La quantité de transcrits codant ce récepteur est deux fois plus importante dans les médulloblastomes que dans les épendymomes. Dans ce dernier type de tumeur, l'ARNm de sst1 est également fortement exprimé. En immunohistochimie, le marquage de sst1 et surtout de sst2A est plus intense dans les médulloblastomes que dans les épendymomes. La localisation observée pour le récepteur sst1 est identique pour les deux types de tumeur et est essentiellement cytoplasmique. En revanche, la localisation de sst2 est essentiellement membranaire pour les médulloblastomes et exclusivement cytoplasmique pour les épendymomes. Aucune corrélation n'est constatée entre l'évolution clinique, l'histologie et l'expression des transcrits des différents récepteurs. In vitro, la somatostatine exerce un effet anti-prolifératif significatif sur la lignée et les cellules tumorales de médulloblastome. La scintigraphie à l'octréotide marqué s'est révélée fiable sur 17 des 23 examens réalisés. Ces résultats ouvrent des perspectives pour le suivi des patients opérés de médulloblastomes et d'épendymomes.LYON1-BU Santé (693882101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Tumor surgery within cerebral eloquent areas: A two-institutions experience

Introduction: Tumor surgery within eloquent areas represents a formidable challenge and the use of electrical cortico-subcortical stimulation mapping (ESM), allows to localize sensorimotor and language areas and pathways. Our aim is to point out methodological issues of ESM and its impact on outcome at the light of a prospective analysis of a two-institution series of 159 patients with lesions involving eloquent areas with a lengthy follow up. Material and Methods: All patients operated on for lesions involving eloquent areas between May 2000 and May 2010 at the Neurosurgical Department of the Neurological and Neurosurgical Hospital 'P. Wertheimer' in Lyon (France) and at the Neurosurgical Department of the University Hospital in Catanzaro (Italy), were enrolled prospectively in our study. Results: Of 159 consecutive patients, 141 of them underwent surgical removal of the lesion with the aid of electrical cortico-subcortical stimulation mapping integrated in a setting of intraoperative localization of anatomic landmarks for eloquent areas. For the remaining 18 patients ESM was not deemed useful or feasible: 15 patients received a biopsy and 3 patients received tumor debulking under general anesthesia. For patients operated with ESM, it was possible to achieve a gross total removal of the lesion in 67,4% of cases (95 patients). One patient died in the immediate postoperative period for a pulmonary embolism. At a total mean follow-up of 62.8 months 78 patients were alive, 62 of which were recurrence free and had a KPS of 70% or more, while the other 80 patients had a mean survival time of 23.9 months, with a mean high quality survival period (KPS ≥ 70) of21.6 months. Discussion and Conclusion: Intraoperative electrical language and motor mapping, when feasible and indicated, consistently localizes eloquent cortical areas and subcortical pathways and allows to set the tumor resection boundaries according to functional limits, with a favorable impact on survival and quality of life. Integration of neurofunctional data with anatomic landmarks is nonetheless useful to expedite the surgical procedure and improve specificity and sensibility of functional mapping

Pituitary Stalk Hemangioblastoma: Complete Resection through Orbitozygomatic Approach with Extradural Anterior Clinoidectomy

Background Pituitary stalk hemangioblastomas (PSHBLs) are rare vascular tumors and their surgical removal is challenging due to the proximity with several fundamental anatomic structures including the pituitary stalk, third ventricle, hypothalamus, and optic pathways. To date, only few descriptions of transcranial and transsphenoidal approaches for PSHBLs have been reported in the literature and none in video, with suboptimal outcomes in terms of pituitary function preservation. Here, we describe the use of orbitozygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC) for the removal of a PSHBL with preservation of the pituitary stalk. Case Description A 60-year-old woman with a sporadic symptomatic HBL of the pituitary stalk, with the typical features of avid contrast enhancement on T1- and flow voids on T2-weighted magnetic resonance imaging (MRI) images, underwent a right OZ craniotomy with EAC. The choice of the approach was guided by the necessity of exposing the floor of the 3rd ventricle and infundibulum, where the origin of the pituitary stalk is better appreciated and preserved, without brain retraction. EAC was deemed important due to the necessity of widening the right carotico-oculomotor and opticocarotid triangles and gaining access to the ophthalmic segment of the internal carotid artery, origin of the superior hypophyseal artery, and the tumor supply. The postoperative MRI confirmed gross tumor removal with preservation of the pituitary stalk and no tumor recurrence after 2 years of follow-up. Conclusion OZ craniotomy coupled with EAC facilitates surgical removal of PSHBLs thus augmenting the chances of pituitary function preservation. The link to the video can be found at https://youtu.be/hH65W937RGY

Spectroscopie de fluorescence de la protoporphyrine IX pour l’assistance peropératoire lors de l’exérèse de gliomes

Présentation oraleNational audienceIntroductionLa fluorescence de la protoporphyrine IX (PpIX) induite par ingestion de 5-ALA peut être utilisée en neurochirurgie, lors de la résection de gliomes, afin de visualiser les tissus tumoraux. Une étude préliminaire a montré (Montcel et al., biomed. Opt. Exp.,2013, 4(4), 548-558) que la PpIX est présente sous deux états dans les gliomes et qu’un rapport de ces deux états dans les biopsies étudiées a permis de différencier le cœur tumoral des glioblastomes de leurs infiltrations et des gliomes de bas grade. Notre but est maintenant d’étudier la faisabilité de l’utilisation peropératoire d’une sonde de spectroscopie de fluorescence afin d’identifier les marges tumorales et, à terme, de quantifier en temps réel la concentration en PpIX puis en cellules cancéreuses dans le tissu sondé.Matériels et méthodes Le prototype développé contient une sonde que le neurochirurgien pose sur le cerveau et qui illumine le tissu et récupère le spectre de fluorescence. L’illumination se fait à différentes longueurs d’onde afin de mieux discriminer in vivo les deux états de la PpIX. Une étude de faisabilité et d’intérêt du prototype est menée sur 10 patients, 5 présentant un gliome de bas grade et 5 un gliome de haut grade.RésultatsLes résultats obtenus confirment la faisabilité de mesures peropératoires. Par ailleurs, la signature spectrale émise par le tissu sondé diffère suivant le grade du gliome et suivant la longueur d’onde d’excitation. Ceci indiquant bien la présence des deux états différents de la PpIX in vivo.Conclusion Le système développé a montré une plus grande sensibilité de détection que le microscope peropératoire, comme attendu dans la littérature. Par ailleurs, les premiers résultats obtenus in vivo sur cerveau humain tendent à confirmer les résultats obtenus in vitro et sur biopsies : l’excitation des deux états de la PpIX par plusieurs longueurs d’onde permettrait de discriminer différentes catégories histologiques

5-aminolevulinic acid–protoporphyrin IX fluorescence-guided surgery of high-grade gliomas : a systematic review

The current first-line treatment of malignant gliomas consists in surgical resection (if possible) as large as possible. The existing tools don’t permit to identify the limits of tumor infiltration, which goes beyond the zone of contrast enhancement on MRI. The fluorescence-guided malignant gliomas surgery was started 15 years ago and had become a standard of care in many countries. The technique is based on fluorescent molecule revelation using the filters, positioned within the surgical microscope. The fluorophore, protoporphyrin IX (PpIX), is converted in tumoral cells from 5-aminolevulinic acid (5-ALA), given orally before surgery. Many studies have shown that the ratio of gross total resections was higher if the fluorescence technique was used. The fluorescence signal intensity is correlated to the cell density and the PpIX concentration. The current method has a very high specificity but still lower sensibility, particularly regarding the zones with poor tumoral infiltration. This book reviews the principles of the technique and the results (extent of resection and survival)