Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.Peer reviewe

Stratégie de restauration de la fonction diaphragmatique après lésion traumatique de la moelle épinière cervicale haute

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Closure strategy for endoscopic pituitary surgery: Experience from 3015 patients.

peer reviewed[en] INTRODUCTION: Effective strategies are required to ensure optimal management of the crucial closure step in endoscopic pituitary surgery. Many surgical techniques have been reported but no significant consensus has been defined. METHODS: Between January 2006 and March 2022, 3015 adult patients with pituitary adenomas were operated on by a single expert neurosurgical team, using a mononostril endoscopic endonasal approach. Based of preoperative risk factors of and operative findings, a detailed closure strategy was used. Body mass index >40, sellar floor lysis, number of surgeries>2, large skull base destruction, prior radiotherapy were considered as preoperative risk factors for closure failure. All patients treated with an expanded endonasal approach were excluded. RESULTS: Patients were mostly women (F/M ratio: 1.4) with a median age of 50 (range: 18 -89). Intraoperative CSF leak requiring specific surgical management was observed in 319/3015 (10.6%) of patients. If intraoperative leak occurred, patients with predictive risk factors were managed using a Foley balloon catheter in case of sellar floor lysis or BMI>40 and a multilayer repair strategy with a vascularized nasoseptal flap in other cases. Postoperative CSF leak occurred in 29/3015 (1%) of patients, while meningitis occurred in 24/3015 (0.8%) of patients. In patients with intraoperative leak, closure management failed in 11/319 (3.4%) of cases. CONCLUSION: Based on our significant 16-year experience, our surgical management is reliable and easy to follow. With a planned and stepwise strategy, the closure step can be optimized and tailored to each patient with a very low failure rate

A unique case of pure lateral spinal cord herniation.

BACKGROUND: Spinal cord herniation (SCH) remains a challenging diagnosis for neuroradiologists and may require treatment challenging for neurosurgeons. Most cord herniations are usually found at anterior thoracic levels. CLINICAL PRESENTATION: A 28-year-old woman presented at our department with a 7-year history of progressive myelopathy. MR analysis showed a displacement of the spinal cord in a lateral thoracic dural defect. The herniated cord was released using a microscope and the patient significantly recovered 6 months after surgery. CONCLUSION: We present a unique case of pure lateral SCH. In the light of reviewed literature and operative findings, the underlying pathophysiological mechanisms are discussed.[Cas unique d’hernie médullaire trans-durale strictement latérale] CONTEXTE : Les hernies médullaires trans-durales restent de diagnostic difficile pour le neuroradiologue et leur traitement constitue un challenge pour le neurochirurgien. La plupart des hernies médullaires sont situées dans un défect dural antérieur, au niveau du rachis thoracique. PRÉSENTATION CLINIQUE : Une patiente de 28 ans s’est présentée dans le service de neurochirurgie avec un tableau clinique de myélopathie, de développement lentement progressif sur une période de 7 ans. L’IRM médullaire a montré une incarcération du cordon médullaire thoracique dans un défect dural strictement latéral. La moelle épinière a été libérée chirurgicalement, sous microscope. L’état neurologique de la patiente s’est significativement amélioré 6 mois après l’intervention. CONCLUSION : Nous présentons un cas unique d’hernie médullaire trans-durale strictement latérale. À la lumière des données de la littérature et de nos constatations opératoires, les mécanismes physiopathologiques sous-jacents sont discutés

A suggested protocol for the endocrine postoperative management of patients undergoing pituitary surgery

International audiencePurpose: Endocrine disorders are the most frequent postoperative complications in patients undergoing pituitary surgery. Given the absence of recent guidelines on the postoperative care following pituitary surgery, this article summarizes the available evidence on the topic. Method: We conducted a systematic search of PubMed up to 2021 and updated the search in December 2022. We retrieved 119 articles and included 53 full-text papers. Results: The early postoperative care consists of the assessment for cortisol deficiency and diabetes insipidus (DI). Experts suggest that all patients should receive a glucocorticoid (GC) stress dose followed by a rapid taper. The decision for GC replacement after discharge depends on the morning plasma cortisol level on day 3 after surgery. Experts suggest that patients with a morning plasma cortisol 18 mcg/dL, the patient can be discharged safely without GC, as suggested by observational studies. Postoperative care also includes a close monitoring of water balance. If DI develops, desmopressin is used only in case of uncomfortable polyuria or hypernatremia. The assessment of other hormones is indicated at 3 months postoperatively and beyond. Conclusion: The evaluation and treatment of patients following pituitary surgery are based on expert opinion and a few observational studies. Further research is needed to provide additional evidence on the most appropriate approach

Is There a Place for the Posterior Approach in Cases of Acute Myelopathy on Thoracic Disc Hernia ?

International audienceBackground: Acute myelopathy in cases of thoracic disc herniation (TDH) is an exceptional condition for which the treatment is not codified. Here we present the results of a standardized procedure in 10 patients who underwent surgery for acute myelopathy on TDH between December 2009 and December 2016.Methods: Our approach began with a cautious laminectomy without resection of the hernia on the day of admission. On subsequent days, a complementary thoracoscopic procedure was performed according to the patient's neurologic recovery and the nature of the hernia (calcified or fibrous). Outcome was assessed by the Frankel score at the last consultation.Results: All patients had acute myelopathy, with Frankel score of C or worse and a TDH detected on magnetic resonance imaging occupying an average of 62.5 ± 18.4% of the canal. This lesion was calcified in 6 cases and soft in 4 cases. The laminectomy allowed stabilization in 1 case and a neurologic improvement in 9 cases. Complementary surgery via a thoracoscopic approach was performed in the 6 cases of calcified hernia. After an average follow-up of 44.55 ± 26.44 months, 6 patients showed complete neurologic recovery and 4 had moderate sequelae (Frankel D).Conclusions: Laminectomy appears to allow stabilization of the neurologic situation in rare cases of acute myelopathy on TDH. The need for complementary resection of the hernia by an anterior approach should always be discussed secondarily

Méningiomes et utilisation prolongée d’acétate de cyprotérone: à propos de 28 cas opérés

Introduction L’acétate de cyprotérone (ACYP) est contre-indiqué en cas de méningiome car il favorise leur développement. L’objectif de l’étude est de déterminer les caractéristiques phénotypiques et génotypiques des patients opérés de méningiomes traités de façon prolongée par ACYP. Méthodes Nous avons analysé en rétrospectif les caractéristiques phénotypiques de 28 patients, traités par ACYP qui ont été opérés de méningiomes dans le service de neurochirurgie de l’hôpital Foch à Suresnes entre 2003 et 2010. La recherche de mutation PIK3CA et TRAF7 a été réalisée chez 18 patientes. Résultats Vingt-huit patients, d’âge moyen 48±6,5 ans, ont été inclus : 27 femmes et 1 homme. Dix-huit présentent un méningiome unique et 10 des méningiomes multiples. Quarante-sept pour cent des méningiomes sont développés dans la région sellaire, 40 % près des lobes cérébraux, 9 % sur la faux du cerveau et 4 % dans la fosse postérieure. La durée de traitement par ACYP a tendance à être plus longue dans le groupe méningiomes multiples que dans le groupe méningiome unique (16 ans 95 % IC[12–19] vs 12 ans 95 IC[9–20] NS, p = 0,29). La dose cumulée estimée d’ACYP tend à être plus élevée en cas de méningiome multiple (276 575 mg ± 406 567 vs 107 585 mg ± 119 231, NS, p = 0,11). Les mutations somatiques sont présentes dans 6/11 méningiomes uniques versus chez tous les méningiomes multiples (p = 0,035). Discussion Les mutations somatiques PIK3CA ou TRAF7 sont significativement associées aux méningiomes multiples ; elles sont présentes chez toutes les patientes. La longue durée d’exposition à l’ACYP s’associe au caractère multiple des méningiomes

Endonasal Endoscopic Odontoidectomy in Ventral Diseases of the Craniocervical Junction: Results of a Multicenter Experience

Background: Over the past decades, supported by preliminary anatomic and clinical studies exploring its feasibility and safety, experience has increased of the use of the endoscopic endonasal approach (EEA) to ventral diseases at the craniocervical junction (CCJ). Methods: A multicenter study was carried out over a 4-year period of 14 patients managed by EEA odontoidectomy for CCJ diseases causing irreducible atlantoaxial dislocation. The surgical setup included an IGS system based on computed tomography and magnetic resonance images fusion, and 0° and 30° angled endoscopes with dedicated endoscopic tools. Results: Nine men and 5 women, with a mean age of 60.7 years, were included. The mean follow-up was 28.5 months; 9 patients had basilar impression, whereas 5 had a degenerative pannus. The quality of anterior decompression was excellent in all cases; nonetheless, a posterior stabilization was deemed necessary in 13 patients, and no external orthosis was used during the postoperative course. No tracheostomy or gastrostomy was required after surgery; no deaths, no new neurologic deficits/complications, and no postoperative cerebrospinal fluid leak were recorded. At follow-up, the neurologic status assessed with Frankel grade did not deteriorate in any of the patients but improved in 13 of them; and no new listhesis was shown on neuroradiologic follow-up. Conclusions: The results show that EEA provides a direct surgical corridor to the CCJ, allowing an adequate decompression as with the more invasive transoral route. Morbidity is less than with a transoral approach, resulting in higher patient comfort and faster recovery. Keywords: Craniocervical junction; Decompression; Endonasal; Endoscopy; Odontoidectomy; Transoral

Medical debulking with BRAF/MEK inhibitors in aggressive BRAF-mutant craniopharyngioma

International audienc