Publications by authors named "Jean Regis"

210 Publications

Stereotactic Radiosurgery for Post-Operative Metastatic Surgical Cavities: A Critical Review and International Society of Stereotactic Radiosurgery (ISRS) Practice Guidelines.

Int J Radiat Oncol Biol Phys 2021 Apr 20. Epub 2021 Apr 20.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Canada.

Purpose: The purpose of this critical review is to summarize the literature specific to single fraction stereotactic radiosurgery (SRS) and multiple fraction stereotactic radiotherapy (SRT) for post-operative brain metastases resection cavities and present practice recommendations on behalf of the ISRS.

Methods And Materials: Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) approach to search for manuscripts reporting SRS/SRT outcomes for post-operative brain metastases tumor bed resection cavities with a search end date of July 20, 2018.  Prospective studies, consensus guidelines, and retrospective series that included exclusively post-operative brain metastases and had at minimum 100 patients were considered eligible.

Results: The Embase and Pubmed search revealed a total of 157 manuscripts of which 77 were selected, and 55 manuscripts of which 23 were selected, for full text screening, respectively. Eight retrospective series, 1 phase II prospective study, 3 randomized controlled trials, and 1 consensus contouring paper were deemed appropriate for inclusion.  The data suggest that SRS/SRT to surgical cavities with prescription doses 30-50 Gy EQD2, 50-70 Gy EQD2, and 70-90 EQD2 are associated with rates of local control ranging from 60.5% to 91% (median 80.5%).  Randomized data suggests improved local control with single fraction SRS compared to observation and improved cognitive outcomes as compared to WBRT.  Toxicity of SRS/SRT in the post-operative setting were limited and reviewed herein.

Conclusions: Although randomized data raise concern for poorer local control following resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses utilized in the SRS arm. Retrospective studies suggest high rates of local control following single fraction SRS and hypofractionated SRT for post-operative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible post-operative patients. Emerging data suggests that fractionated SRT may provide superior local control compared to single fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a pre-operative diameter greater than 2.5 cm.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.016DOI Listing
April 2021

Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

Neuromodulation 2021 Apr 22. Epub 2021 Apr 22.

Department of Neurosurgery, Université Côte d'Azur, CHU de Nice, Nice, France.

Introduction: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement.

Materials And Methods: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second.

Results: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261).

Discussion: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions.

Conclusion: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.
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http://dx.doi.org/10.1111/ner.13394DOI Listing
April 2021

Long-term cognitive outcome after radiosurgery in epileptic hypothalamic hamartomas and review of the literature.

Epilepsia 2021 Apr 20. Epub 2021 Apr 20.

Department of Functional and Stereotactic Neurosurgery and Gamma Knife Radiosurgery, Timone University Hospital, Aix-Marseille University, Marseille, France.

Objective: Epileptic patients with hypothalamic hamartoma (HH) frequently present cognitive impairments. Surgical techniques aiming at HH can be very efficient for epilepsy relief and cognitive improvement but are also demonstrated to carry a significant risk of additional reduction in memory function in these already disabled patients. Gamma knife radiosurgery (GKS) offers an efficient minimally invasive procedure. We evaluated the effect of stereotactic radiosurgery on cognitive outcome.

Methods: We designed a prospective single-center case series study. Thirty-nine epileptic patients (median age = 17 years, range = 4-50) with HH underwent preoperative and postoperative testing of intelligence quotient (IQ; all patients), including a working memory component, and other memory function testing (for patients ≥16 years old). All patients were prospectively evaluated and underwent complete presurgical and postsurgical clinical, electrophysiological, endocrinal, and visual assessments. In all patients, the postoperative assessment was performed at least 3 years after radiosurgery. We explored what variables correlate with cognitive outcome. Literature review was done for other surgical techniques and their risks for cognitive complications after surgery.

Results: No decline was observed in intellectual ability (including working memory) after GKS, and no memory decline was seen in adults. We observed significant improvement (>1 SD in z-score) in working memory index (46%) and processing speed index (35%), as well as improvement in full-scale IQ (24%), verbal comprehension index (11%), perceptual organization index (21%), verbal learning (20%), and visual learning (33%). Before GKS, the probability of seizure cessation was higher in patients with higher cognitive performance. After GKS, the cognitive improvement was significantly higher in the seizure-free patients compared to the non-seizure-free patients.

Significance: We found clear cognitive improvement in a high percentage of patients but importantly no significant decline in intellectual ability (including working memory) and no decline in memory in adult patients 3 years after GKS. GKS compares favorably to the other surgical techniques in terms of cognitive outcome, with similar seizure freedom.
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http://dx.doi.org/10.1111/epi.16896DOI Listing
April 2021

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis.

Neurosurg Rev 2021 Apr 13. Epub 2021 Apr 13.

Department of Clinical Neurosciences, Neurosurgery Service and Gamma Knife Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Vestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2-3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44-64). The median marginal dose prescribed at first SRS was 12 Gy (range 8-24) and at second SRS was 12 Gy (range 9.8-19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2-39%, I = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7-75.1%, I = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5-29.7%, I = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4-18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4-7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8-83.8%, I = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.
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http://dx.doi.org/10.1007/s10143-021-01528-yDOI Listing
April 2021

Epileptic hypothalamic hamartomas impact of topography on clinical presentation and radiosurgical outcome.

Epilepsy Res 2021 Jul 23;173:106624. Epub 2021 Mar 23.

Department of Functional and Stereotactic Neurosurgery and Gamma Knife, Timone University Hospital, Aix-Marseille University, Marseille, France; Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France.

Introduction: Evidence exists for the role of the hypothalamic hamartoma's topography as a determinant for the clinical presentation. How the hamartoma relation to the hypothalamic structures can make clinical presentations, severity and surgery outcomes different from patient to patient is largely unknown. Our aim was to analyze the effect of fine anatomical topography on clinical spectrum and radiosurgery outcome.

Methods: Forty-eight epileptic patients with hypothalamic hamartoma were treated by Gamma Knife Surgery and were reviewed for fine topography and morphology using magnetic resonance neuroimaging. We evaluated different topographic patterns; contact to prominent structures (the mammillary body, tuber cinereum and pituitary stalk), the degree of involvement within sagittally-oriented regions, (mammillary, tuberal, and supra optic) coronally-oriented zones (periventricular, medial, and lateral), lesion dimensions (length, width, and height),and volumes (total, intra-hypothalamic, and extra-hypothalamic volumes). This data were statistically analysed for correlation with all clinical variables and epilepsy surgery outcome. We reviewed all the classification protocols in the literature.

Results: Focal onset impaired awareness seizures started at an earlier age of onset with larger hypothalamic hamartoma volume and dimensions. Lateral extension within the hypothalamus was associated with more severe epilepsy, higher seizure frequency, more severe psychiatric comorbidity, hetero-aggression, hyperkinesia, and school difficulties. Presence of precocious puberty was positively correlated to anterior-posterior extension; tuberal region involvement, hypothalamic hamartoma volume, and type III-VI. Larger hypothalamic hamartoma presented precocious puberty at an earlier age of onset. After Gamma Knife Surgery, epilepsy outcome was better and rapid when lesion is smaller. Post-radiosurgical transient increased seizures were present when the mammillary region was more involved.

Conclusion: Clinical presentation of epileptic hypothalamic hamartoma is significantly affected by fine topography patterns and invaded hypothalamic areas. Gamma Knife Radiosurgery effect is better and rapid in smaller hamartoma (Type I-III) and seizure outcome was not affected by the invaded hypothalamic areas.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106624DOI Listing
July 2021

The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol.

Stereotact Funct Neurosurg 2021 Mar 8:1-6. Epub 2021 Mar 8.

Stereotactic and Functional Neurosurgery Service and Gamma Knife Unit, CHU Timone, Marseille, France.

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot's targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and 18F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim's circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.
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http://dx.doi.org/10.1159/000514066DOI Listing
March 2021

Clinical evaluation of a real-time inverse planning for Gamma Knife radiosurgery by convex optimization: a prospective comparative trial in a series of vestibular schwannoma patients.

Acta Neurochir (Wien) 2021 04 5;163(4):981-989. Epub 2021 Jan 5.

Institut de Neuroscience des Systèmes, Functional Neurosurgery and Radiosurgery Department, Aix-Marseille Université, Hôpital de la Timone, APHM, Marseille, France.

Background: Gamma Knife radiosurgery (GKRS) inverse dose planning is currently far from competing effectively with the quality of dose planning developed by experienced experts. A new inverse planning (IP) method based on « efficient convex optimization algorithms » is proposed, providing high-quality dose plans in real time.

Materials And Methods: Eighty-six patients treated by GKRS for vestibular schwannomas (VS) were recruited. The treatment plans created by the first author, who has 27 years of experience and has developed and delivered more than 15,000 dose plans, served as reference. A first set of basic constraints determined by default led the IP for an initial real-time dose plan. Additional constraints were interactively proposed by the planner to take other parameters into account. A second optimized plan was then calculated by the IP. The primary endpoint was the Paddick Conformity Index (PCI). The statistical analysis was planned on a non-inferiority trial design. Coverage, selectivity, and gradient indexes, dose at the organ(s) at risk, and 12 Gy isodose line volume were compared.

Results: After a single run of the IP, the PCI was shown to be non-inferior to that of the "expert." For the expert and the IP, respectively, the median coverage index was 0.99 and 0.98, the median selectivity index 0.92 and 0.90, the median gradient index 2.95 and 2.84, the median dose at the modiolus of the cochlea 2.83 Gy and 2.86 Gy, the median number of shots 14.31 and 24.13, and the median beam-on time 46.20 min and 26.77 min. In a few specific cases, advanced tools of the IP were used to generate a second run by adding new constraints either globally (for higher selectivity) or locally, in order to increase or decrease these constraints focally.

Conclusion: These preliminary results showed that this new IP method based on « efficient convex optimization algorithms », called IntuitivePlan®, provided high-quality dose plans in real time with excellent coverage, selectivity, and gradient indexes with optimized beam-on time. If the new IP evaluated here is able to compete in real time with the quality of the treatment plans of an expert with extensive radiosurgical experience, this could allow new planners/radiosurgeons with limited or no experience to immediately provide patients with high-quality GKRS for benign and malignant lesions.
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http://dx.doi.org/10.1007/s00701-020-04695-xDOI Listing
April 2021

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review.

Cancer Metastasis Rev 2021 Mar 4;40(1):341-354. Epub 2021 Jan 4.

Département de radiothérapie-oncologie, bâtiment Atrium, Clinique Pasteur, 1, rue de la Petite-Vitesse, 31300, Toulouse, France.

Stereotactic radiosurgery (SRS) is a standard option for brain metastases (BM). There is lack of consensus when patients have a systemic treatment, if a washout is necessary. The aim of this review is to analyze the toxicity of SRS when it is concurrent with chemotherapies, immunotherapy, and/or targeted therapies. From Medline and Embase databases, we searched for English literature published up to April 2020 according to the PRISMA guidelines, using for key words the list of the main systemic therapies currently in use And "radiosurgery," "SRS," "GKRS," "Gamma Knife," "toxicity," "ARE," "radiation necrosis," "safety," "brain metastases." Studies reporting safety or toxicity with SRS concurrent with systemic treatment for BM were included. Of 852 abstracts recorded, 77 were included. The main cancers were melanoma, lung, breast, and renal carcinoma. These studies cumulate 6384 patients. The median SRS dose prescription was 20 Gy [12-30] .For some, they compared a concurrent arm with a non-concurrent or a SRS-alone arm. There were no skin toxicities, no clearly increased rate of bleeding, or radiation necrosis with significant clinical impact. SRS combined with systemic therapy appears to be safe, allowing the continuation of treatment when brain SRS is considered.
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http://dx.doi.org/10.1007/s10555-020-09949-9DOI Listing
March 2021

Tumor control and trigeminal dysfunction improvement after stereotactic radiosurgery for trigeminal schwannomas: a systematic review and meta-analysis.

Neurosurg Rev 2020 Nov 13. Epub 2020 Nov 13.

Neurosurgery and Neurooncology Service, Centre Hospitalier Regional Universitaire de Lille, Roger Salengro Hospital, Lille, France.

Trigeminal nerve schwannomas (TS) are uncommon intracranial tumors, frequently presenting with debilitating trigeminal and/or oculomotor nerve dysfunction. While surgical resection has been described, its morbidity and mortality rates are non-negligible. Stereotactic radiosurgery (SRS) has emerged with variable results as a valuable alternative. Here, we aimed at reviewing the medical literature on TS treated with SRS so as to investigate rates of tumor control and symptomatic improvement. We reviewed manuscripts published between January 1990 and December 2019 on PubMed. Tumor control and symptomatic improvement rates were evaluated with separate meta-analyses. This meta-analysis included 18 studies comprising a total of 564 patients. Among them, only one reported the outcomes of linear accelerators (Linac), while the others of GK. Tumor control rates after SRS were 92.3% (range 90.1-94.5; p < 0.001), and tumor decrease rates were 62.7% (range 54.3-71, p < 0.001). Tumor progression rates were 9.4% (range 6.8-11.9, p < 0.001). Clinical improvement rates of trigeminal neuralgia were 63.5% (52.9-74.1, p < 0.001) and of oculomotor nerves were 48.2% (range 36-60.5, p < 0.001). Clinical worsening rate was 10.7% (range 7.6-13.8, p < 0.001). Stereotactic radiosurgery for TS is associated with high tumor control rates and favorable clinical outcomes, especially for trigeminal neuralgia and oculomotor nerves. However, patients should be correctly advised about the risk of tumor progression and potential clinical worsening. Future clinical studies should focus on standard reporting of clinical outcomes.
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http://dx.doi.org/10.1007/s10143-020-01433-wDOI Listing
November 2020

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

Mol Psychiatry 2021 01 3;26(1):60-65. Epub 2020 Nov 3.

Department of Neurosurgery, Karolinska Institutet and University Hospital, Stockholm, Sweden.

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.
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http://dx.doi.org/10.1038/s41380-020-00933-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815503PMC
January 2021

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

Neurosurgery 2021 01;88(2):375-383

Université Côte d'Azur, FHU INOVPAIN, CHU de Nice, Nice, France.

Background: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series.

Objective: To evaluate ONS long-term efficacy in rCCH.

Methods: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption.

Results: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%).

Conclusion: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.
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http://dx.doi.org/10.1093/neuros/nyaa373DOI Listing
January 2021

Trigeminal Neuralgia Secondary to Meningiomas and Vestibular Schwannoma Is Improved after Stereotactic Radiosurgery: A Systematic Review and Meta-Analysis.

Stereotact Funct Neurosurg 2021 9;99(1):6-16. Epub 2020 Sep 9.

Centre Hospitalier Regional Universitaire de Lille, Roger Salengro Hospital, Lille, France,

Introduction: Trigeminal neuralgia (TN) secondary to tumors is encountered in up to 6% of patients with facial pain syndromes and is considered to be associated with tumors affecting the trigeminal nerve pathways. The most frequent are meningiomas and vestibular schwannomas (VS). Stereotactic radiosurgery (SRS) has emerged as a valuable treatment, with heterogeneity of clinical results. We sought to review the medical literature on TN treated with SRS for meningiomas and VS and investigate the rates of improvement of TN symptoms.

Methods: We reviewed articles published between January 1990 and December 2019 in PubMed. Pain relief after SRS, the maintenance of pain relief, and TN recurrence and complications were evaluated with separate meta-analyses, taking into account the data on individual patients.

Results: Pain relief after SRS was reported as Barrow Neurological Institute (BNI) pain intensity scores of BNI I in 50.5% (range 36-65.1%) of patients and BNI I-IIIb in 83.8% (range 77.8-89.8%). There was no significant difference in series discussing outcomes for tumor targeting versus tumor and nerve targeting. Recurrences were described in 34.7% (range 21.7-47.6; tumor targeting). Maintenance of BNI I was reported in 36.4% (range 20.1-52.7) and BNI I-IIIb in 41.2% (range 29.8-52.7; tumor targeting series). When both the nerve and the tumor were targeted, only 1 series reported 86.7% with BNI I-IIIb at last follow-up. Complications were encountered in 12.6% (range 6.3-18.8; tumor targeting series) of patients; however, they were much higher, as high as 26.7%, in the only study reporting them after targeting both the nerve and the tumor. The most common complication was facial numbness.

Conclusion: SRS for TNB secondary to benign tumors, such as meningiomas and VS, is associated with favorable clinical course, but less favorable than in idiopathic TN. There was, however, heterogeneity among reports and targeting approaches. Although targeting both the nerve and the tumor seemed to achieve better long-term results, the rate of complications was much higher and the number of patients treated was limited. Future clinical studies should focus on the standard reporting of clinical outcomes and randomization of targeting methods.
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http://dx.doi.org/10.1159/000509842DOI Listing
September 2020

Completion Corpus Callosotomy with Stereotactic Radiosurgery for Drug-Resistant, Intractable Epilepsy.

World Neurosurg 2020 11 20;143:440-444. Epub 2020 Aug 20.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address:

Background: Stereotactic radiosurgery (SRS) offers a noninvasive technique for division of the corpus callosum, which can confer improved seizure control to patients suffering from frequent atonic seizures due to rapid interhemispheric generalization. This noninvasive approach is well-suited for use in a palliative intervention for improved seizure control in this patient population. To our knowledge, this is the first report of radiosurgical completion corpus callosotomy in an adult in the United States.

Case Description: A 20-year-old ambidextrous nonverbal man with a history of refractory generalized epilepsy status post open anterior corpus callosotomy at age 10 years, Lennox-Gastaut syndrome, and autism presented after 2 years of incremental, progressive deterioration in seizure control and behavior including 1 year. The family decided to pursue SRS corpus callosotomy. Under general anesthesia, a volume of interest encompassing a full midsagittal plane of the corpus callosum was defined to deliver 60 Gy to the 50% isodose line fully encompassing the target. Gamma Knife was used with 2 isocenters at 90° and 1 at 110° and isodose lines of 60, 20, and 12 Gy. Treatment was carried out without difficulty or complications while the patient remained under close monitoring. The patient was discharged the next day with a 2-week taper of dexamethasone.

Conclusions: Eight months postradiosurgical corpus callosotomy, the patient is free of atonic seizures and is ambulatory. In carefully selected cases and with protective radiosurgical planning, SRS for completion corpus callosotomy represents an effective option for refractory seizure control.
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http://dx.doi.org/10.1016/j.wneu.2020.08.102DOI Listing
November 2020

Effective posterior extension of callosotomy by gamma knife surgery.

Epileptic Disord 2020 Jun;22(3):342-348

Department of Functional and Stereotactic Neurosurgery and Gamma Knife Radiosurgery, Timone University Hospital, Marseille, France, Aix Marseille Université, Inserm, L'Institut de Neurosciences des Systèmes (INS, UMR1106), Marseille, France.

Drop attacks are the most responsive seizure type to open callosotomy, however, surgical complications can worsen the prognosis. Various less invasive techniques have been explored in an effort to minimize the risk. We present a patient who suffered from life-threatening traumatizing drop attacks in whom previous open anterior callosotomy and vagal nerve stimulation were unsatisfactory. Following posterior extension of the callosotomy by non-invasive gamma knife surgery, the rate of drop attacks declined from 30 a day to once a day, or every few days over a four-month period, without complications. Open callosotomy is an invasive and high risk treatment option for patients with drop attacks. The procedure has a potential for complications and neurological consequences that can worsen the functional capacity of a patient who already suffers with disability. Recently, in an attempt to decrease the invasiveness associated with this technique, additional technical refinements and less invasive procedures have been explored in a few studies. Here, we report a case of refractory epilepsy with life-threatening traumatizing DA, in which the patient was treated by radiosurgical posterior callosotomy after unsatisfactory open anterior callosotomy and vagal nerve stimulation.
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http://dx.doi.org/10.1684/epd.2020.1170DOI Listing
June 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

Stereotactic Radiosurgery for Intracranial Noncavernous Sinus Benign Meningioma: International Stereotactic Radiosurgery Society Systematic Review, Meta-Analysis and Practice Guideline.

Neurosurgery 2020 10;87(5):879-890

Department of Neurosurgery, Unit of Radiotherapy, Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italia.

Background: Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment.

Objective: To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Methods: Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched.

Results: Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low.

Conclusion: The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.
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http://dx.doi.org/10.1093/neuros/nyaa169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566438PMC
October 2020

Stereotactic Radiosurgery for Spetzler-Martin Grade I and II Arteriovenous Malformations: International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.

Neurosurgery 2020 09;87(3):442-452

Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota.

Background: No guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs).

Objective: To establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥10 grade I-II AVMs with a follow-up of ≥24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included Spetzler-Martin parameters, dosimetric variables, and "excellent" outcomes (defined as total obliteration without new post-SRS deficit).

Results: Of 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs.

Conclusion: The literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.
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http://dx.doi.org/10.1093/neuros/nyaa004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426190PMC
September 2020

The outcomes of a second and third Gamma Knife radiosurgery for recurrent essential glossopharyngeal neuralgia.

Acta Neurochir (Wien) 2020 02 17;162(2):271-277. Epub 2019 Dec 17.

Stereotactic and Functional Neurosurgery Service and Gamma Knife Unit, Assistance Publique-Hôpitaux de Marseille, Centre Hospitalier Universitaire La Timone, Marseille, France.

Introduction: Gamma Knife radiosurgery (GKR) is a minimally invasive surgical option for drug-resistant essential glossopharyngeal neuralgia (GPN). The authors reviewed pain outcomes and complications in GPN patients who underwent a second or a third GKR for recurrent or persistent pain.

Methods: A retrospective review of all patients treated in a single center (Marseille, France) since 2004 was performed. Median prescribed dose was 85 Gy (range 70-90 Gy) at second GKR and 85 Gy at third GKR. Clinical outcome was evaluated using the Barrow Neurological Institute (BNI) scale.

Results: Six patients (4 males, 2 females) underwent second or third GKR. The median age was 70.2 years (range 64-83 years) at second GKR and 79.8 years at third GKR. No patient had any previous surgery but GKR. Five cases had a neurovascular conflict. Median follow-up period was 12 months (range 10-94 months) after second GKR and 16 months after third GKR. The median delay to initial pain freedom response was 30 days (range 3-120 days). One patient experienced pharyngeal hypoesthesia after second GKR. After a third GKR, up to 16 months, no side effects were encountered. At the last follow-up, 3 patients were BNI I, 2 were BNI IIIa, and one did not have any improvement.

Conclusions: Second GKR resulted in pain reduction with low risk of additional morbidity. In patients unsuitable for microvascular decompression, GKR as a repeat or third treatment for intractable GPN is safe and effective. Third GKR was not associated with any side effects up to 16 months after the procedure.
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http://dx.doi.org/10.1007/s00701-019-04124-8DOI Listing
February 2020

Graph theory analysis of resting-state functional magnetic resonance imaging in essential tremor.

Hum Brain Mapp 2020 04 15;41(6):1689-1694. Epub 2019 Dec 15.

Medical Image Processing Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

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http://dx.doi.org/10.1002/hbm.24900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268027PMC
April 2020

Connectivity strength, time lag structure and the epilepsy network in resting-state fMRI.

Neuroimage Clin 2019 23;24:102035. Epub 2019 Oct 23.

CNRS, CRMBM, Aix Marseille Univ., France; AP-HM, CHU Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France; Institut de Neurosciences des Systèmes, Aix Marseille Univ., Inserm UMR 1106, INS, France; Clinical Neurophysiology, APHM, Hôpital de la Timone, Marseille, France.

The relationship between the epilepsy network, intrinsic brain networks and hypersynchrony in epilepsy remains incompletely understood. To converge upon a synthesized understanding of these features, we studied two elements of functional connectivity in epilepsy: correlation and time lag structure using resting state fMRI data from both SEEG-defined epileptic brain regions and whole-brain fMRI analysis. Functional connectivity (FC) was analyzed in 15 patients with epilepsy and 36 controls. Correlation strength and time lag were selected to investigate the magnitude of and temporal interdependency across brain regions. Zone-based analysis was carried out investigating directed correlation strength and time lag between both SEEG-defined nodes of the epilepsy network and between the epileptogenic zone and all other brain regions. Findings were compared between patients and controls and against a functional atlas. FC analysis on the nodal and whole brain levels identifies consistent patterns of altered correlation strength and altered time lag architecture in epilepsy patients compared to controls. These patterns include 1) broadly distributed increased strength of correlation between the seizure onset node and the remainder of the brain, 2) decreased time lag within the seizure onset node, and 3) globally increased time lag throughout all regions of the brain not involved in seizure onset or propagation. Comparing the topographic distribution of findings against a functional atlas, all resting state networks were involved to a variable degree. These local and whole brain findings presented here lead us to propose the network steal hypothesis as a possible mechanistic explanation for the non-seizure clinical manifestations of epilepsy.
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http://dx.doi.org/10.1016/j.nicl.2019.102035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881607PMC
September 2020

Stereotactic radiosurgery for non-functioning pituitary adenomas: meta-analysis and International Stereotactic Radiosurgery Society practice opinion.

Neuro Oncol 2020 03;22(3):318-332

Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Background: This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.

Methods: Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words "radiosurgery" and "pituitary" and/or "adenoma." Weighted random effects models were used to calculate pooled outcome estimates.

Results: Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5-35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12-25 Gy, delivered in 3-5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0-96.0%) and 97.0% (95% CI: 93.0-98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0-88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0-27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0-7%).

Conclusions: SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
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http://dx.doi.org/10.1093/neuonc/noz225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058447PMC
March 2020

Letter: Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas.

Neurosurgery 2020 02;86(2):E252-E253

Department of Clinical Neurosciences Neurosurgery Service and Gamma Knife Center Lausanne University Hospital (CHUV) Lausanne, Switzerland.

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http://dx.doi.org/10.1093/neuros/nyz503DOI Listing
February 2020

Establishment of a Therapeutic Ratio for Gamma Knife Radiosurgery of Trigeminal Neuralgia: The Critical Importance of Biologically Effective Dose Versus Physical Dose.

World Neurosurg 2020 Feb 10;134:e204-e213. Epub 2019 Oct 10.

Functional and Stereotaxic Neurosurgery Service and Gamma Knife Unit, Centre Hospitalier Universitaire "La Timone," Marseille, France.

Objective: How variations of treatment time affect the safety and efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. With the relative simplicity of treatment planning for trigeminal neuralgia (TN), this question has been addressed in a group of these patients. Using the concept of the biologically effective dose (BED), the effect of the two key variables, dose and treatment time, were considered.

Methods: A retrospective analysis was performed of 408 TN cases treated from 1997 to 2010. Treatment involved the use of a single 4 mm isocenter. If conditions allowed, the isocenter was placed at a median distance of 7.5 mm from the emergence of the trigeminal nerve from the brain stem. The effects were assessed in terms of the incidence of the complication, hypoesthesia, and in terms of efficacy using the incidence of pain free after 30 days and 1 and 2 years. These responses were evaluated with respect to both the physical dose and the BED, the latter using a bi-exponential repair model.

Results: RE-evaluation showed that the prescription doses, at the 100% isodose, varied from 75 to 97.9 Gy, delivered in 25-135 minutes. The relationship between the physical dose and the incidence of hypoesthesia was not significant; the overall incidence was ∼20%. However, a clear relationship was found between the BED and the incidence of hypoesthesia, with the incidence increasing from <5% after a BED of ∼1800 Gy to 42% after ∼2600 Gy. Efficacy, in terms of freedom from pain, was ∼90%, irrespective of the BED (1550-2600 Gy) at 1 and 2 years. The data suggested that "pain free" status developed more slowly at lower BED values.

Conclusions: These results strongly suggest that safety and efficacy might be better achieved by prescribing a specific BED instead of a physical dose. A dose and time to BED conversion table has been prepared to enable iso-BED prescriptions. This finding could dramatically change dose-planning strategies in the future. However, this concept requires validation for other indications for which more complex dose planning is required.
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http://dx.doi.org/10.1016/j.wneu.2019.10.021DOI Listing
February 2020

Thalamotomy for tremor normalizes aberrant pre-therapeutic visual cortex functional connectivity.

Brain 2019 11;142(11):e57

Medical Image Processing Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

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http://dx.doi.org/10.1093/brain/awz299DOI Listing
November 2019

"Plis de passage" Deserve a Role in Models of the Cortical Folding Process.

Brain Topogr 2019 11 3;32(6):1035-1048. Epub 2019 Oct 3.

Neurospin, CEA, Paris-Saclay University, 91191, Gif-sur-Yvette, France.

Cortical folding is a hallmark of brain topography whose variability across individuals remains a puzzle. In this paper, we call for an effort to improve our understanding of the pli de passage phenomenon, namely annectant gyri buried in the depth of the main sulci. We suggest that plis de passage could become an interesting benchmark for models of the cortical folding process. As an illustration, we speculate on the link between modern biological models of cortical folding and the development of the Pli de Passage Frontal Moyen (PPFM) in the middle of the central sulcus. For this purpose, we have detected nine interrupted central sulci in the Human Connectome Project dataset, which are used to explore the organization of the hand sensorimotor areas in this rare configuration of the PPFM.
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http://dx.doi.org/10.1007/s10548-019-00734-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882753PMC
November 2019

Letter: A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

Neurosurgery 2019 12;85(6):E1125-E1126

Department of Clinical Neurosciences Neurosurgery Service and Gamma Knife Center Lausanne University Hospital (CHUV) Lausanne, Switzerland.

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http://dx.doi.org/10.1093/neuros/nyz371DOI Listing
December 2019

EANO guideline on the diagnosis and treatment of vestibular schwannoma.

Neuro Oncol 2020 01;22(1):31-45

Department of Neurosurgery Ludwig-Maximilians University and DKTK partner site, University of Munich, Munich, Germany.

The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy.
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http://dx.doi.org/10.1093/neuonc/noz153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954440PMC
January 2020

Does NF2 status impact the results of combined surgery and adjunctive Gamma Knife surgery for large vestibular schwannomas?

Neurosurg Rev 2020 Aug 6;43(4):1191-1199. Epub 2019 Aug 6.

Department of Neurosurgery, North University Hospital, APHM-AMU, Chemin des Bourrely, 13015, Marseille, France.

In order to verify whether neurofibromatosis type 2 (NF2) could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we compared a group of NF2 patients operated with a facial nerve-sparing technique to a group of sporadic VSs of similar volume that underwent the same treatment regimen in the same period. Single-center retrospective cohort study about 12 consecutive NF2 and 69 non-NF2 patients operated on for large VS between September 2006 and November 2016. After resection, patients were allocated to an upfront Gamma Knife surgery policy of the tumor residue. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 92% of the NF2 and 83% of the non-NF2 patients (p = .90). The median volume of tumor residue was .92 cc in the NF2 group and .54 cc in the non-NF2 group (p = .14). Tumor control was achieved in 83% and 81% of cases in the NF2 and the non-NF2 populations, respectively, with a mean follow-up of 73 months in both groups. The 1-, 5-, and 7-year progression-free survival were 92%, 83%, and 83% respectively in the NF2 group, and 99%, 83%, and 80% in the non-NF2 group (p = .96). Our analysis of 12 NF2 and 69 non-NF2 patients operated on by the same surgical team with the same treatment regimen did not show any functional or tumor control difference between those groups.
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http://dx.doi.org/10.1007/s10143-019-01143-yDOI Listing
August 2020