Publications by authors named "Henry Dufour"

97 Publications

Crossed brainstem syndrome revealing bleeding brainstem cavernous malformation: an illustrative case.

BMC Neurol 2021 May 20;21(1):204. Epub 2021 May 20.

Department of Neurosurgery, Timone University Hospital, APHM, 264 rue Saint-Pierre, 13005, Marseille, France.

Background: Since the nineteenth century, a great variety of crossed brainstem syndromes (CBS) have been described in the medical literature. A CBS typically combines ipsilateral cranial nerves deficits to contralateral long tracts involvement such as hemiparesis or hemianesthesia. Classical CBS seem in fact not to be so clear-cut entities with up to 20% of patients showing different or unnamed combinations of crossed symptoms. In terms of etiologies, acute brainstem infarction predominates but CBS secondary to hemorrhage, neoplasm, abscess, and demyelination have been described. The aim of this study was to assess the proportion of CBS caused by a bleeding episode arising from a brainstem cavernous malformation (BCM) reported in the literature.

Case Presentation: We present the case of a typical Foville syndrome in a 65-year-old man that was caused by a pontine BCM with extralesional bleeding. Following the first bleeding episode, a conservative management was decided but the patient had eventually to be operated on soon after the second bleeding event.

Discussion: A literature review was conducted focusing on the five most common CBS (Benedikt, Weber, Foville, Millard-Gubler, Wallenberg) on Medline database from inception to 2020. According to the literature, hemorrhagic BCM account for approximately 7 % of CBS. Microsurgical excision may be indicated after the second bleeding episode but needs to be carefully weighted up against the risks of the surgical procedure and openly discussed with the patient.

Conclusions: In the setting of a CBS, neuroimaging work-up may not infrequently reveal a BCM requiring complex multidisciplinary team management including neurosurgical advice.
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http://dx.doi.org/10.1186/s12883-021-02223-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136125PMC
May 2021

Ipsilateral vs controlateral approach in tuberculum sellae meningiomas surgery: a retrospective comparative study.

Neurosurg Rev 2021 Apr 22. Epub 2021 Apr 22.

Department of Neurosurgery, Timone University Hospital, APHM-AMU, 264 Rue Saint-Pierre, 13385, Marseille, France.

Most of tuberculum sellae meningiomas (TSM) show asymmetric growth. They are usually resected through ipsilateral approaches. The access of the inferior-medial side of the ipsilateral optic nerve might be challenging, which result in increased manipulation of the compromised optic nerve. The contralateral approach has been described to avoid these technical difficulties. Assessing the long-term visual and olfactory outcome, as well as recurrence rate in patients operated for TSM through ipsilateral or contralateral approaches. Single center retrospective cohort study about 94 patients operated on between March 2000 and April 2018. Seventy percent of the preoperative visual acuity loss totally resolved (44%) or showed varying degrees of improvement (26%) after surgery. Seventy-two percent of the preoperative visual field defects evolved favorably (44% recovery, 28% improvement). Eight patients showed aggravated visual disturbances (9%). A contralateral approach seemed to be predictive of visual field defects improvement after surgery (OR = 0.4), with borderline significant results (p = .08). There was a higher rate of postoperative olfactory nerve impairment after a contralateral approach (37% vs 17%, p = .03). Total removal of the tumor fragment entering the optic canal was accomplished in 96% in the contralateral vs 75% in the ipsilateral group (p = .04). The 2-, 5-, and 7-year tumor progression-free survival were 100% in the Simpson grade 2 group, and 85% (n = 17), 74% (n = 11), and 67% (n = 5) in the Simpson grade 4 group, respectively (p = .00). Resection of tuberculum sellae meningiomas through a contralateral approach seems to provide better visual outcome and tumor control at the cost of increased olfactory nerve disorders.
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http://dx.doi.org/10.1007/s10143-021-01536-yDOI Listing
April 2021

Robotic Assistance for Minimally Invasive Cervical Pedicle Instrumentation: Report on Feasibility and Safety.

World Neurosurg 2021 Jun 5;150:e777-e782. Epub 2021 Apr 5.

Department of Neurosurgery, La Timone University Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France; Spine Unit, La Timone University Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Background: Accurate screw placement remains challenging, especially in the cervical spine. We present our first experience of minimally invasive posterior cervical and upper thoracic pedicle screw fixation in the lower cervical spine.

Methods: This study reports a case series of patients, undergoing posterior percutaneous pedicle fixation using Cirq robotic assistance coupled to the Airo intraoperative computed tomography scan and Brainlab navigation system. Routine computed tomography was performed on postoperative day 2 to evaluate pedicle screw placement. The effective dose was calculated.

Results: Between February 2020 and December 2020, 7 patients (4 men and 3 women) were treated. The mean age was 58.8 years (range, 29-75 years). Fixation was performed with a cannulated PASS OCT Reconstruction System (Medicrea). Overall, 28 screws were placed within cervical and upper thoracic pedicles. According to the Neo and Heary classification, 85.7% were rated as acceptable and 14.3% as poor. The radiation dose received by the patient was 9.1 mSv (range, 7.7-10.6 mSv). The radiation dose received by the surgical staff was 0 mSv. The postoperative course was excellent.

Conclusions: Posterior miniopen fixation using Cirq robotic assistance coupled with an intraoperative computed tomography navigation system is a major innovation that can improve the accuracy of pedicle screw positioning, with acceptable patient radiation and reduced surgical team exposure.
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http://dx.doi.org/10.1016/j.wneu.2021.03.150DOI Listing
June 2021

Post-operative complications in cranial and spine neurosurgery: a prospective observational study.

J Neurosurg Sci 2021 Mar 11. Epub 2021 Mar 11.

Department of Neurosurgery, Aix-Marseille Université, APHM, CHU Timone, Marseille, France.

Background: Post-operative complications do occur in all neurosurgical departments, but the way they are defined, and their true incidence vary a lot. The aim of the present study is to objectively assess the morbidity and mortality related to all neurosurgical procedures performed in our department and provide insight on their main causes and identify key factors to reduce their incidence.

Methods: Data were retrieved from a prospectively-maintained database regarding all patients undergoing a cranial or spinal neurosurgical procedure between November 2016 and April 2016 in the neurosurgical department in Timone University Hospital (APHMMarseille). Patients undergoing a functional, pediatric or interventional neuroradiological procedures were not included.

Results: The medical records of a total number of 963 patients were analyzed. A postoperative complication occurred in 208 patients (21.6%) including 115 (26.6%) in the cranial surgery group and 93 (17.5%) in the spinal surgery group. A complication occurred 1.5 more frequently in the cranial than in the spinal surgery group. Cranial surgery is 1.5 times more at risk of complications than spinal surgery (p=0.007). Preoperative comorbidities (ASA score > 3 to 4) were significantly associated with the occurrence of complications (p<.001). In the cranial group, procedures performed in an emergency setting were 1.8 times more at risk of complications than scheduled surgeries (p<.001). Conversely, in the spine group, scheduled surgeries were 1.4 times less at risk than emergency procedures (p=0.04). The main complication in both groups was found to be post-operative infection, with an incidence of 9.3% and 11.1% for cranial and spinal surgery respectively. Post-operative mortality reached 4.9% and 1.7% and the average length of stay was 12 and 11 days respectively.

Conclusions: The incidence of complication in our series was found to be relatively high with predominantly infection as the main cause of postoperative complications. Reinforcing good practice measures at every step should help to significantly decrease our complication rate.
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http://dx.doi.org/10.23736/S0390-5616.21.05083-9DOI Listing
March 2021

Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells.

Pituitary 2021 Jun 12;24(3):351-358. Epub 2021 Jan 12.

Laboratoire de Biologie Moléculaire et Biochimie, Aix Marseille University, APHM, Marseille Medical Genetics, Inserm U1251, Hôpital de la Conception, Marseille, France.

Context: Somatostatin (SST) and dopamine (DA) inhibit growth hormone (GH) secretion and proliferation of GH-secreting pituitary adenomas (GHomas) through binding to SSTR2 and D2R receptors. Chimeric SST-DA compounds (Dopastatins) display increased potency in inhibiting GH secretion, as compared with individual SST or DA analogs (alone or combined).

Objective: To assess the efficacy of a second-generation dopastatin, TBR-065, in suppressing GH secretion from human GH- and GH/prolactin(PRL)-omas.

Design: We compared the ability of TBR-065 to inhibit GH secretion from primary cultures of human GH- or GH/PRLoma cells to that of the first generation dopastatin, TBR-760 (formerly BIM-23A760), octreotide (OCT) and cabergoline (CAB), the later either alone or combined. We investigated whether there was any impact of BIM-133, the metabolite of TBR-065, on the ability of TBR-065 to inhibit GH in these cultures.

Methods: 17 GH- and GH/PRLomas were included in this study. Inhibition of GH secretion by TBR-065, TBR-760, OCT and CAB (0.1 pM to 0.1 µM) was assessed over a period of 8 h.

Results: All tumors expressed SSTR2 and D2R mRNAs. GH suppression was higher with TBR-065 as compared with TBR-760 (E = 57 ± 5.6% vs. 41.1 ± 12.5%, respectively, p < 0.001) or with OCT + CAB (E = 56.8 ± 7.2% vs. 44.4 ± 9.4%, p < 0.001). BIM-133 did not have any impact on the activity of TBR-065.

Conclusion: TBR-065 has significantly improved efficacy in suppressing GH secretion as compared to current available therapies and may represent a new promising option for the treatment of acromegaly.
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http://dx.doi.org/10.1007/s11102-020-01113-4DOI Listing
June 2021

The risks of medical treatment of prolactinoma.

Ann Endocrinol (Paris) 2021 Feb 26;82(1):15-19. Epub 2020 Dec 26.

Service d'endocrinologie, hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France; Aix Marseille université, centre de références maladies rares HYPO, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

First-line treatment of prolactinoma is usually medical, based on dopamine agonists receptors, mainly cabergoline. The classical side-effects of cabergoline (low blood pressure and nausea) have been well known since it was first introduced. Other side-effects, however, are more controversial or simply less frequent, but need to be considered during monitoring. This review will focus on these side-effects: cardiac valvular fibrosis, pleural, pericardial and retroperitoneal fibrosis, addictive/compulsive behaviors, and risks secondary to significantly decreased tumor volume. We will also describe how such side-effects should be monitored and managed. In our opinion, the low prevalence of these side-effects should not cast doubt on the role of cabergoline in the therapeutic algorithm of prolactinoma.
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http://dx.doi.org/10.1016/j.ando.2020.12.008DOI Listing
February 2021

Chiasmapexy for secondary empty sella syndrome: diagnostic and therapeutic considerations.

Pituitary 2021 Apr 2;24(2):292-301. Epub 2020 Nov 2.

Neurosurgery Department, Hôpital Lariboisiere, APHP, Université Paris Diderot, Paris, France.

Purpose: Secondary empty sella syndrome (SESS) following pituitary surgery remains a diagnostic and therapeutic challenge. The aim of this study was to specify the diagnostic criteria, surgical indications and results of chiasmapexy in the SESS.

Methods: Three cases from two experienced neurosurgical centers were collected and the available literature was reviewed.

Results: The 3 patients were operated for a giant non-functioning pituitary adenoma, a cystic macroprolactinoma, and an arachnoid cyst respectively. Postoperative visual outcome was initially improved, and then worsened progressively. At the time of SESS diagnosis, visual field defect was severe in all cases with optic nerve (ON) atrophy in 2 cases. Patients were operated via an endoscopic endonasal extradural approach. One patient was re-operated because of early fat reabsorption. Visual outcome improved in 1 case and stabilized in 2 cases. Statistical analyses performed on 24 cases from the literature review highlighted that patient age and severity of the preoperative visual defect were respectively significant and nearly significant prognostic factors for visual outcome, unlike the surgical technique.

Conclusion: T2-weighted or CISS/FIESTA sequence MRI is mandatory to visualize adhesions, ON kinking and neurovascular conflict. TS approach is the most commonly used approach. The literature review could not conclude on the need for an intra or extradural approach suggesting case by case adapted strategy. Intrasellar packing with non-absorbable material such as bone should be considered. Severity of the visual loss clearly decreases the visual outcome suggesting early chiasmapexy. In case of severe and long standing symptoms before surgery, benefits and surgical risks should be carefully balanced.
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http://dx.doi.org/10.1007/s11102-020-01104-5DOI Listing
April 2021

Correction to: Molecular revolution in the diagnosis of microbial brain abscesses.

Eur J Clin Microbiol Infect Dis 2020 Dec;39(12):2481

URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Aix-Marseille Université, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille cedex 05, France.

An erratum to this paper has been published: https://doi.org/10.1007/s10096-020-04047-8.
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http://dx.doi.org/10.1007/s10096-020-04047-8DOI Listing
December 2020

Cirq® Robotic Assistance for Minimally Invasive C1-C2 Posterior Instrumentation: Report on Feasibility and Safety.

Oper Neurosurg (Hagerstown) 2020 Jul 25. Epub 2020 Jul 25.

Department of neurosurgery, La Timone university hospital, APHM, Marseille, France.

Background: Accurate screw placement remains very challenging especially in the upper cervical spine.

Objective: To present our first experience of a percutaneous posterior C1-C2 fixation for a traumatic fracture.

Methods: This is a case report of a non-neurological patient, harboring a type II odontoid fracture. She underwent a posterior percutaneous fixation using Cirq® Robotic Assistance coupled to the AIRO® intraoperative computed tomography (iCT)-scan and BrainLab® navigation system (all by BrainLab AG). Routine CT was performed on postoperative day 2 to evaluate pedicle screw placement. The effective dose was calculated.

Results: The C1-C2 posterior percutaneous fixation was performed with cannulated VERTEX® Reconstruction System (Medtronic). Overall, 4 screws were placed. All of them were rated as acceptable (100%). Radiation dose received by the patient was 4.13 mSv. Radiation dose received by the surgical staff was 0 mSv. Postoperative course was excellent.

Conclusion: Posterior percutaneous fixation using Cirq® Robotic Assistance coupled with iCT navigation system is a major innovation that can improve pedicle screw positioning's accuracy with acceptable patient radiation and reduced surgical team exposure.
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http://dx.doi.org/10.1093/ons/opaa208DOI Listing
July 2020

Parasellar Meningiomas.

Neuroendocrinology 2020 3;110(9-10):780-796. Epub 2020 Jun 3.

Department of Neurosurgery, University Hospital of Erlangen, Erlangen, Germany.

Parasellar spaces remain particularly singular, comprising the most important neurovascular structures such as the internal carotid artery and optic, oculomotor, and trigeminal nerves. Meningiomas are one of the most frequent tumors arising from parasellar spaces. In this location, meningiomas remain mostly benign tumors with WHO grade I and a meningothelial subtype. Progestin intake should be investigated and leads mostly to conservative strategies. In the case of benign nonsymptomatic tumors, observation should be proposed. Tumor growth will lead to the proposition of surgery or radiosurgery. In the case of an uncertain diagnosis and an aggressive pattern, a precise diagnosis is required. For cavernous sinus and Meckel's cave lesions, complete removal is rarely considered, leading to the proposition of an endoscopic endonasal or transcranial biopsy. Optic nerve decompression could also be proposed via these approaches. A case-by-case discussion about the best approach is recommended. A transcranial approach remains necessary for tumor removal in most cases. Vascular injury could lead to severe complications. Cerebrospinal fluid leakage, meningitis, venous sacrifice, visual impairment, and cranial nerve palsies are more frequent complications. Pituitary dysfunctions are rare in preoperative assessment and in postoperative follow-up but should be assessed in the case of meningiomas located close to the pituitary axis. Long-term follow-up is required given the frequent incomplete tumor removal and the risk of delayed recurrence. Radiosurgery is relevant for small and well-limited meningiomas or intra-cavernous sinus postoperative residue, whereas radiation therapy and proton beam therapy are indicated for large, extended, nonoperable meningiomas. The place of the peptide receptor radionuclide therapyneeds to be defined. Targeted therapy should be considered in rare, recurrent, and aggressive parasellar meningiomas.
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http://dx.doi.org/10.1159/000509090DOI Listing
June 2020

Spine Surgical Procedures during Coronavirus Disease 2019 Pandemic: Is It Still Possible to Take Care of Patients? Results of an Observational Study in the First Month of Confinement.

Asian Spine J 2020 Jun 8;14(3):336-340. Epub 2020 May 8.

Unité de Chirurgie Rachidienne, Aix-Marseille Université, APHM, CNRS, ISM, CHU Timone, Marseille, France.

Study Design: Observational study.

Purpose: The actual sanitary crisis led to a massive mobilization of the sanitary system toward intensive care units and management of coronavirus disease 2019 (COVID-19) patients. However, some patients still require spinal interventions. The present study aimed to assess the impact of the COVID-19 pandemic on spine surgical in a moderate COVID-19 cluster region.

Overview Of Literature: Previous studies have reported screening and management of patients with spinal conditions during the COVID-19 pandemic. However, to date, knowledge, no observational study on spine surgeries during the pandemic has not been reported.

Methods: Between March 17, 2020 and April 17, 2020, information on spine surgical activity was prospectively collected at our institution. This surgical activity related to the first month of confinement in France was compared to the activity during the same period in 2019 to evaluate the impact of the COVID-19 pandemic on surgical activities.

Results: In order to reduce the contamination rate of patients and medical staff during hospitalization, the spine department was completely reorganized. Non-urgent elective spine surgeries were cancelled. When considering the global amount of surgeries procedures during the first month of confinement, a decrease of almost 50% was observed in the number of surgical procedures. During the study period, 62 patients were eligible for spine surgery. The numbers of patients managed for tumor and infectious cases were stable, while a considerable reduction was observed in the number of trauma and degenerative cases. During the follow-up period, two patients were tested as COVID+ during the postoperative course, and no cases of medical or paramedical staff contamination were reported using polymerase chain reaction-testing.

Conclusions: During the COVID-19 pandemic, it is possible to maintain spine surgical activity. Each surgical procedure must be discussed and organized with all the caregivers involved. Indications for surgery must be in line with the scientific guidelines and adapted to each healthcare facility.
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http://dx.doi.org/10.31616/asj.2020.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280921PMC
June 2020

Surgical management of craniopharyngiomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section.

Acta Neurochir (Wien) 2020 05 28;162(5):1159-1177. Epub 2020 Feb 28.

Department of Neurosurgery, University Hospital of Lausanne, Lausanne, Switzerland.

Background And Objective: Craniopharyngiomas are locally aggressive neuroepithelial tumors infiltrating nearby critical neurovascular structures. The majority of published surgical series deal with childhood-onset craniopharyngiomas, while the optimal surgical management for adult-onset tumors remains unclear. The aim of this paper is to summarize the main principles defining the surgical strategy for the management of craniopharyngiomas in adult patients through an extensive systematic literature review in order to formulate a series of recommendations.

Material And Methods: The MEDLINE database was systematically reviewed (January 1970-February 2019) to identify pertinent articles dealing with the surgical management of adult-onset craniopharyngiomas. A summary of literature evidence was proposed after discussion within the EANS skull base section.

Results: The EANS task force formulated 13 recommendations and 4 suggestions. Treatment of these patients should be performed in tertiary referral centers. The endonasal approach is presently recommended for midline craniopharyngiomas because of the improved GTR and superior endocrinological and visual outcomes. The rate of CSF leak has strongly diminished with the use of the multilayer reconstruction technique. Transcranial approaches are recommended for tumors presenting lateral extensions or purely intraventricular. Independent of the technique, a maximal but hypothalamic-sparing resection should be performed to limit the occurrence of postoperative hypothalamic syndromes and metabolic complications. Similar principles should also be applied for tumor recurrences. Radiotherapy or intracystic agents are alternative treatments when no further surgery is possible. A multidisciplinary long-term follow-up is necessary.
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http://dx.doi.org/10.1007/s00701-020-04265-1DOI Listing
May 2020

Fluctuation analysis of postoperative secretory status in patients operated for acromegaly.

Ann Endocrinol (Paris) 2020 Feb 19;81(1):11-17. Epub 2019 Dec 19.

Neurosurgery department, CHU Timone, Aix-Marseille university, AP-HM, Marseille, France; Inserm, MMG, Aix-Marseille university, Marseille, France.

Objective: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly.

Methods: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively).

Results: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome.

Conclusions: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.
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http://dx.doi.org/10.1016/j.ando.2019.11.002DOI Listing
February 2020

Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial.

Clin Cancer Res 2020 02 22;26(3):552-557. Epub 2020 Jan 22.

Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie, Marseille, France.

Purpose: Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect . The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas.

Patients And Methods: Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety.

Results: A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months ( < 0.0002) and 0.48%/3 months at 6 months after treatment ( < 0.0003).

Conclusions: The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2109DOI Listing
February 2020

Minimally Invasive Percutaneous C1-C2 Fixation Using an Intraoperative Three-Dimensional Imaging-Based Navigation System for Management of Odontoid Fractures.

World Neurosurg 2020 05 19;137:266-271. Epub 2019 Dec 19.

Departments of Neurosurgery, La Timone University Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France; Spine Unit, La Timone University Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Background: Odontoid fractures are the most common lesions of the upper cervical spine in patients >70 years old. These fractures are associated with frequent comorbidities, and minimally invasive techniques might have the potential to reduce postoperative complications while ensuring better precision. The aim of this study was to report an innovative technique and preliminary results of minimally invasive atlantoaxial fixation using a three-dimensional intraoperative navigation system and percutaneous approach.

Methods: This retrospective study included 5 consecutive patients with an acute traumatic odontoid type II fracture managed using a percutaneous Harms fixation under three-dimensional intraoperative navigation guidance.

Results: C1 lateral mass screws and C2 isthmus screws were successfully placed in all patients. In all cases (100%), adequate screw positioning with no medial breach and no transverse foramen obstruction was observed. No intraoperative complications, such as injury of the vertebral artery, spinal nerve root, or spinal cord, occurred. None of the 5 patients received blood transfusion during or after the procedure. During the follow-up period (mean, 11.2 months; range, 5-16 months), 4 patients (80%) demonstrated a favorable clinical recovery, and only 1 patient required occasional medication for moderate pain. Mean radiation exposure was 4.83 mSV for each patient and 0 mSv for surgical staff.

Conclusions: Minimally invasive atlantoaxial fixation using an intraoperative three-dimensional navigation system is a safe and effective alternative to the conventional approach that reduces postoperative morbidity.
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http://dx.doi.org/10.1016/j.wneu.2019.12.054DOI Listing
May 2020

Surgical indications for pituitary tumors during pregnancy: a literature review.

Pituitary 2020 Apr;23(2):189-199

Neurosurgery Department, Aix-Marseille Univ, APHM, CHU Timone, La Timone Hospital, 264 rue Saint-Pierre, 13005, Marseille, France.

Purpose: Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks.

Methods: A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy.

Results: Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit.

Conclusion: Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.
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http://dx.doi.org/10.1007/s11102-019-01004-3DOI Listing
April 2020

Interfascial approach for pterional craniotomy: technique and adjustments to prevent cosmetic complications.

Acta Neurochir (Wien) 2019 11 6;161(11):2353-2357. Epub 2019 Sep 6.

Department of Neurosurgery, La Timone Hospital, APHM, Aix Marseille University, 264 Rue Saint Pierre, 13385, Marseille, France.

Background: Interfascial dissection for pterional craniotomy is one of the main techniques to expose the pterional region.

Method: A step-by-step optimized method of interfascial dissection to avoid three main esthetic complications of the pterional approach-upper facial nerve palsy, temporal muscle atrophy, and retro-orbital depression. A video of the interfascial dissection and three artistic drawings are provided in support of this technique.

Conclusion: A safe method of interfascial dissection, respecting anatomy, and avoiding cosmetic complications has been proposed.
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http://dx.doi.org/10.1007/s00701-019-04058-1DOI Listing
November 2019

Ophthalmoplegic complications in transsphenoidal pituitary surgery.

J Neurosurg 2019 Jul 26:1-9. Epub 2019 Jul 26.

1Department of Neurosurgery, La Timone University Hospital, and.

Objective: Ophthalmoplegia is a rare complication of transsphenoidal surgery, only noted in a few studies. The purpose of this study was to analyze the complications of cranial nerve III, IV, or VI palsy after transsphenoidal surgery for pituitary adenoma and understand its physiopathology and outcome.

Methods: The authors retrospectively analyzed 24 cases of postoperative ophthalmoplegia selected from the 1694 patients operated via a transsphenoidal route in their department.

Results: Two patients were operated on via microscopy and 22 via endoscopy. Patients operated on endoscopically had a greater risk of presenting with an extraocular nerve deficit postoperatively (p = 0.0115). It was found that an extension into or an invasion of the cavernous sinus (Knosp grade 3 or 4 on MRI, 18/24 patients) was correlated with a higher risk of postoperative ophthalmoplegia (p < 0.0001). The deficit was apparent immediately after surgery in 2 patients. For these 2 patients, the mechanisms of ophthalmoplegia were compression or intraoperative nerve lesion. The other 22 patients became symptomatic in the 12-72 hours following the surgery. The mechanisms implied in these cases were intrasellar compressive hematoma (4/22 cases), intracavernous hemorrhagic suffusion, or incomplete resection of the intracavernous portion of the tumor. All patients who did not present with oculomotor palsy immediately after surgery completely recovered their deficits in the 3 months that followed, while the other 2 experienced permanent damage.

Conclusions: Extraocular nerve dysfunction after transsphenoidal pituitary surgery is a rare complication that occurs more frequently in the case of the invasion or an important extension into the cavernous sinus. In this series, it also appears to be significantly more frequent in patients operated on via an endoscopic approach. Most patients have deficits that appear with a delay of 12-72 hours postoperatively and they are most likely to completely recover.
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http://dx.doi.org/10.3171/2019.5.JNS19782DOI Listing
July 2019

Letter to the Editor: "Why We Should Still Treat by Neurosurgery Patients With Cushing Disease and a Normal or Inconclusive Pituitary MRI".

J Clin Endocrinol Metab 2019 12;104(12):5791-5792

Department of Endocrinology, Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, et Assistance Publique-Hôpitaux de Marseille, Marseille, France.

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http://dx.doi.org/10.1210/jc.2019-01183DOI Listing
December 2019

Clinical presentation, treatment and outcome of IgG4-related pachymeningitis: From a national case registry and literature review.

Semin Arthritis Rheum 2019 12 15;49(3):430-437. Epub 2019 May 15.

Aix-Marseille Univ, APHM, Médecine Interne, Hôpital de la Timone, Marseille, France. Electronic address:

Pachymeningitis is rare, either idiopathic or secondary to inflammatory disorders, after tumoral, surgical or infectious causes have been excluded. The fibroinflammatory IgG4-related disease is one of the etiologies of pachymeningitis with only few cases reported yet. From a single referral regional center, we evaluated the frequency of IgG4-related disease as the cause of inflammatory pachymeningitis in 10% of cases. From a National case registry of IgG4-related disease the pachymeningitis frequency was 4.1%. We report eight new cases with cranial, spinal or both involvements and a literature review of 46 pathological proven cases. We observed that IgG4-related pachymeningitis is in most cases not associated to extra-neurological manifestations of the disease. Only 27% of spinal and 40% of cranial IgG4-related pachymeningitis are associated with other disease localizations. First line treatment strategies included surgery and steroids. The use of immunosuppressants or rituximab was necessary in 18% of spinal and 54% of cranial localizations. Some patients remained with sequellae and clinical and/or radiological improvement can be difficult to obtain.
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http://dx.doi.org/10.1016/j.semarthrit.2019.05.003DOI Listing
December 2019

Clinical management of difficult to treat macroprolactinomas.

Expert Rev Endocrinol Metab 2019 05 27;14(3):179-192. Epub 2019 Mar 27.

a Marseille Medical Genetics, Inserm U1251, Hôpital de la Conception, Service d'Endocrinologie , Aix Marseille Univ, APHM , Marseille , France.

Introduction: Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist (DA) such as cabergoline, their management becomes problematic since a resistance to DA can occur and/or if the tumor displays features of aggressiveness, two conditions that are closely related.

Areas Covered: Epidemiology and medical treatment of prolactinomas; resistance to DA and molecular basis of DA-resistance; therapeutical alternatives in case of DA-resistant Prolactinomas and therapies in development; summarizing conclusions.

Expert Opinion: The management of DA-resistant prolactinomas requires a multidisciplinary approach by an expert team. Along with discussions about surgery with or without gamma knife radiosurgery, genetic screening for multiple endocrine neoplasia type 1 (MEN1) syndrome is actively discussed in a case-by-case approach. In case of surgery, a careful analysis of the tumor sample can provide information about its aggressivity potential according to recent criteria. Ultimately, temozolomide can be indicated if the tumor is rapidly growing and/or threatening for the patient.
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http://dx.doi.org/10.1080/17446651.2019.1596024DOI Listing
May 2019

Correction to: Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

J Neurooncol 2019 May;142(3):521

Aix-Marseille Univ, CNRS UMR 7051, INP, Inst Neurophysiopathol, Marseille, France.

In the initial, online publication, the authors' given names were captured as family names and vice versa. The names are correctly shown here. The original article has been corrected.
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http://dx.doi.org/10.1007/s11060-019-03141-yDOI Listing
May 2019

Functioning gonadotroph adenoma with severe ovarian hyperstimulation syndrome: A new emergency in pituitary adenoma surgery? Surgical considerations and literature review.

Ann Endocrinol (Paris) 2019 Apr 7;80(2):122-127. Epub 2019 Feb 7.

Department of neurosurgery, hôpital La Timone, Assistance publique-Hôpitaux de Marseille (AP-HM), Marseille, France; Aix-Marseille université, institut national de la santé et de la recherche médicale (Inserm), U1251, Marseille medical genetics (MMG), Marseille, France.

The authors reported 2 cases of functioning gonadotroph pituitary adenoma (FGPA) revealed by an ovarian hyperstimulation syndrome (OHSS) in young women. In the first case, OHSS was observed after GnRH analog injection. Pelvic echography revealed multiple voluminous ovarian cysts. Dopamine agonist posology failed in estradiol hypersecretion control, which necessitated endoscopic endonasal transsphenoidal surgery. The patient experienced improvement in pelvic pain as estradiol hypersecretion decreased during the first few postoperative days. Outcome was favorable, and her menstrual cycle was normal after two months. The second case was a young girl with spontaneous pelvic pain and elevated plasma FSH and estradiol levels. FGPA was confirmed on cerebral MRI. Dopamine agonists were introduced, and surgical removal of the pituitary tumor was scheduled for 7 days later. In the meantime, the patient was admitted and underwent surgery for bilateral adnexal torsion related to OHSS. The pituitary tumor was removed one week later. Outcome was favorable, and estradiol and FSH plasma levels were normal after 3 months. The ovarian cysts were no longer visible on echography after 3 months. Given the lack of efficacy of the current standard medical therapy, surgical removal of pituitary adenomas is the reference treatment for FGPA. The authors suggest that severe OHSS related to FGPA should be considered as a relative surgical emergency and that surgery should not be unduly delayed, given the unpredictable risk of adnexal torsion, particularly in case of voluminous ovarian cysts. The authors performed a literature review on this topic.
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http://dx.doi.org/10.1016/j.ando.2018.11.007DOI Listing
April 2019

Neuro-radiological characteristics of adult diffuse grade II and III insular gliomas classified according to WHO 2016.

J Neurooncol 2019 May 11;142(3):511-520. Epub 2019 Feb 11.

Aix-Marseille Univ, CNRS UMR 7051, INP, Inst Neurophysiopathol, Marseille, France.

Introduction: The phenotypic heterogeneity of diffuse gliomas is still inconsistently explained by known molecular abnormalities. Here, we report the molecular and radiological features of diffuse grade WHO II and III gliomas involving the insula and its potential impact on prognosis.

Methods: Clinical, pathological, molecular and neuro-radiological features of 43 consecutive patients who underwent a surgical resection between 2006 and 2013 for a grade II and III gliomas involving the insula was retrospectively analyzed.

Results: Median age was 44.4 years. Eight patients had oligodendrogliomas, IDH mutant (IDH) and 1p/19q-codeleted (6 grade II, 2 grade III). Twenty-eight patients had diffuse astrocytomas, IDH (22 grade II and 6 grade III) and seven patients had grade II diffuse astrocytomas, IDH (A-IDH). Vimentin staining was exclusively recorded in tumor cells from A-IDH (p = 0.001). Mean cerebral blood volume (CBV) (p = 0.018), maximal value of CBV (p = 0.017) and ratio of the corrected CBV (p = 0.022) were lower for A-IDH. Volumetric segmentation of ADC allowed the identification of the tumor cores, which were smaller in A-IDH (p < 0.001). The tumor occurrences of A-IDH were exclusively located into the temporo-insular region. Median progression-free survival (PFS) and overall survival (OS) were 50.9 months (95% CI: 26.7-75.0) and 80.9 months (60.1-101.6). By multivariate analysis, A-IDH (p = 0.009; p = 0.019), 7p gain and 10q loss (p = 0.009; p = 0.016) and vimentin positive staining (p = 0.011; p = 0.029) were associated with poor PFS and OS respectively.

Conclusions: Insular low-grade A-IDH presented with poor prognosis despite a smaller tumor core and no evidence of increased perfusion on MR imaging.
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http://dx.doi.org/10.1007/s11060-019-03122-1DOI Listing
May 2019

Leptomeningeal Gliomatosis: A Single Institution Study of 31 Patients.

Anticancer Res 2019 Feb;39(2):1035-1041

Department of Neuro-Oncology, AP-HM, CHU Timone, Marseille, France.

Background/aim: Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG.

Patients And Methods: We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9).

Results: Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p<0.001), a prolonged interval from the initial glioma diagnosis (IGD) to LG diagnosis (p=0.003), BCNU-TMZ as the preferred first-line treatment for LG out of the three options (p=0.008), and Karnofsky performance status (KPS) ≥70 (p=0.012). Prolonged interval from IGD to LG diagnosis (HR=5.839) and BCNU-TMZ as the chosen first-line treatment for LG (HR=6.635) remained significant in the multivariate analyses as well. Among the 22 treated patients, the median OS was significantly higher (p=0.008) with the BCNU-TMZ treatment (5.7 months; 95%CI=4.2-7.1), compared to other types of treatment offered (2 months; 95%CI=1.1-2.9).

Conclusion: The time interval from the IGD to the LG diagnosis is a potential prognostic factor for LG. BCNU-TMZ may be a therapeutic option in the present setting.
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http://dx.doi.org/10.21873/anticanres.13210DOI Listing
February 2019

Prospective Comparative Study in Spine Surgery Between O-Arm and Airo Systems: Efficacy and Radiation Exposure.

World Neurosurg 2018 Oct 3;118:e175-e184. Epub 2018 Jul 3.

Department of Neurosurgery, La Timone University Hospital, Marseille, France; Spine Unit, La Timone University Hospital, Marseille, France.

Objective: Pedicle screw placement remains challenging. The present study focuses on the comparison between 2 intraoperative-based neuronavigation systems (O-Arm and AIRO) during thoracolumbar screw instrumentation.

Methods: This is a prospective, comparative, nonrandomized study conducted in 2 French academic centers. The O-Arm was used at the University Hospital of Bordeaux, whereas the AIRO was used at the University Hospital of Marseille. Routine computed tomography was performed on postoperative day 2 to evaluate pedicle screw placement. Measures of radiation exposure were extracted directly from reports provided by each system. The effective dose was calculated.

Results: Overall, 74 screws were placed in 11 patients in the O-Arm group and 84 in 11 patients in the AIRO group. In the first group, 90.8% were rated as acceptable and 92.2% in the second (P > 0.05) according to the Heary and Gertzbein classifications, respectively, for thoracic and lumbar spine. Differences between both implantation systems were significant (P < 0.05) concerning dose length product (235 and 1039 mGy/cm, in O-Arm and AIRO, respectively), overall mean radiation dose received by 1 patient (3.52 and 15.6 mSv in O-Arm and AIRO, respectively), mean radiation dose per single scan (2.58 and 8.7 mSv in O-Arm and AIRO, respectively), mean effective dose per instrumented level (1.04 and 3.9 mSv in O-Arm and AIRO, respectively), and radiation dose received by the primary surgeon (0.63 and 0 μSv in O-Arm and AIRO, respectively).

Conclusions: Intraoperative computed tomography-based navigation is a major innovation that improves the accuracy of pedicle screw positioning with acceptable patient radiation exposure and reduced surgical team exposure.
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http://dx.doi.org/10.1016/j.wneu.2018.06.148DOI Listing
October 2018

Intracranial Giant Mycotic Aneurysm without Endocarditis and Vasculitis: Report of Rare Entity and Review of Literature.

World Neurosurg 2018 Nov 23;119:353-357. Epub 2018 Aug 23.

APHM, CHU Timone, Department of Neurosurgery, Marseille, France; Aix Marseille University, APHM, CNRS, CRN2M, Marseille, France.

Background: Infectious aneurysm is a rare complication in intracranial aneurysm. Moreover, giant aneurysm is a rare entity in intracranial aneurysm. In the great majority of infectious intracranial aneurysms, vasculitis and/or endocarditis is associated.

Case Description: Here, we report the case of an 83-year-old man who developed a giant infectious intracranial aneurysm on the anterior communicating artery. This patient had never shown any intracranial bleeding. A surgery was performed, and purulent liquid and aneurysm wall were removed during procedure. The bacteriologic analyses reported Campylobacter fetus.

Conclusions: This bacterium seems to be more and more frequent in North America and Europe, according to the current literature. Moreover, cases of mycotic extracranial aneurysm were reported. Here we report the first case of intracranial giant infectious aneurysm in an adult patient, without any endocarditis or vasculitis. This new entity could be the cause of a bacterial graft on an asymptomatic giant preexisting intracranial aneurysm or a consequence of campylobacteriosis.
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http://dx.doi.org/10.1016/j.wneu.2018.08.086DOI Listing
November 2018

Robot-assisted multi-level anterior lumbar interbody fusion: an anatomical study.

Acta Neurochir (Wien) 2018 10 24;160(10):1891-1898. Epub 2018 Jul 24.

Department of Spine Surgery, Timone University Hospital, Marseille, France.

Background: Minimally invasive surgical approaches still provide limited exposure. Access to the L2-L5 intervertebral discs during a single procedure is challenging and often requires repositioning of the patient and adopting an alternative approach.

Objectives: Investigate the windows to the L2-L5 intervertebral discs to assess the dimensions of the interbody implants suitable for the procedure and evaluate the feasibility of multi-level lumbar intervertebral disc surgery in robot-assisted surgery (RAS) METHODS: Sixteen fresh-frozen cadaveric specimens underwent a retroperitoneal approach to access the L2-L5 intervertebral discs. The L2-L3 to L4-L5 windows were defined as the distance between the left lateral border of the aorta (or nearest common iliac vessel) and the medial border of the psoas, measured in a static state and after gentle medial retraction of the vascular structures. Two living porcine specimens and one cadaveric specimen underwent da Vinci robot-assisted transperitoneal approach to expose the L2-L3 to L4-L5 intervertebral discs and perform multi-level discectomy and interbody implant placement.

Results: The L2-L3 to L4-L5 intervertebral disc windows significantly increased from a static to a retracted state (p < 0.05). The mean L2-L3, L3-L4, and L4-L5 windows measured respectively 20.1, 21.6, and 19.6 mm in the static state, and 27.2, 30.9, and 30.3 mm after gentle vascular retraction. The intervertebral windows from L2-L3 to L4-L5 were successfully exposed through an anterior transperitoneal approach with the da Vinci robot on the cadaveric and living porcine specimens, and interbody implants were inserted.

Conclusion: RAS appears to be feasible for a mini-invasive multi-level lumbar intervertebral disc surgery. The RAS procedure, longer and more expensive than conventional MIS approaches, should be reserved for elective patients.
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http://dx.doi.org/10.1007/s00701-018-3621-xDOI Listing
October 2018