Improvement of diffusion tensor imaging-based tractography by free-water correction in nonedematous gliomas: assessment with brain mapping.

OBJECTIVE: The free-water correction algorithm (Freewater Estimator Using Interpolated Initialization [FERNET]) can be applied to standard diffusion tensor imaging (DTI) tractography to improve visualization of subcortical bundles in the peritumoral area of highly edematous brain tumors. Interest in its use for presurgical planning in purely infiltrative gliomas without peritumoral edema has never been evaluated. Using subcortical maps obtained with direct electrostimulation (DES) in awake surgery as a reference standard, the authors sought to 1) assess the accuracy of preoperative DTI-based tractography with FERNET in a series of nonedematous glioma patients, and 2) determine its potential usefulness in presurgical planning. METHODS: Based on DES-induced functional disturbances and tumor topography, the authors retrospectively reconstructed the putatively stimulated bundles and the peritumoral tracts of interest (various associative and projection pathways) of 12 patients. The tractography data obtained with and without FERNET were compared. RESULTS: The authors identified 21 putative tracts from 24 stimulation sites and reconstituted 49 tracts of interest. The number of streamlines of the putative tracts crossing the DES area was 26.8% higher (96.04 vs 75.75, p = 0.016) and their volume 20.4% higher (13.99 cm3 vs 11.62 cm3, p < 0.0001) with FERNET than with standard DTI. Additionally, the volume of the tracts of interest was 22.1% higher (9.69 cm3 vs 7.93 cm3, p < 0.0001). CONCLUSIONS: Free-water correction significantly increased the anatomical plausibility of the stimulated fascicles and the volume of tracts of interest in the peritumoral area of purely infiltrative nonedematous gliomas. Because of the functional importance of the peritumoral zone, applying FERNET to DTI could have potential implications on surgical planning and the safety of glioma resection.

Somatotopy of the sensory thalamus: inputs from directional deep brain stimulation in pain patients.

OBJECTIVE: The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using directional VP deep brain stimulation (DBS) in patients treated for chronic neuropathic pain. METHODS: Six patients with central (four) or peripheral (two) neuropathic pain were treated by VP DBS using directional leads in a prospective study (clinicaltrials.gov NCT03399942). Lead-DBS toolbox was used for leads localization, visualization, and modeling of the volume of tissue activated (VTA). Stimulation was delivered in each direction, 1 month after surgery and correlated to the location of stimulation-induced paresthesias. The somatotopy was modeled by correlating the respective locations of paresthesias and VTAs. We recorded 48 distinct paresthesia maps corresponding to 48 VTAs (including 36 related to directional stimulation). RESULTS: We observed that, in each patient, respective body representations of the trunk, upper limb, lower limb, and head were closely located around the lead. These representations differed across patients, did not follow a common organization and were not concordant with the previously described somatotopic organization of the sensory thalamus. INTERPRETATION: Thalamic reorganization has been reported in chronic pain patients compared to non-pain patients operated for movement disorders in previous studies using intraoperative recordings and micro-stimulation. Using a different methodology, namely 3D representation of the VTA by the directional postoperative stimulation through a stationary electrode, our study brings additional arguments in favor of a reorganization of the VP thalamic somatotopy in patients suffering from chronic neuropathic pain of central or peripheral origin.

Application accuracy of Neuromate robot-guided deep brain stimulation procedures using the non-invasive frameless Neurolocate registration system.

OBJECTIVE: to measure the in vivo application accuracy of Neuromate robot-assisted deep brain stimulation procedures (DBS) using the new, non-invasive, frameless Neurolocate registration method. METHODS: Neurolocate accuracy was measured in 17 patients undergoing DBS (32 leads). The registration was obtained by automatic recognition of the spatial location of the Neurolocate fiducials, fixed on the robot arm, on 3D intraoperative computerized tomography (CT) images relative to the patient's skull contours. Application accuracy was measured as the Euclidian distance between the points theoretically targeted on preoperative magnetic resonance imagingand the tip of the guiding tube visible on intraoperative CT images after merging images. RESULTS: Mean robot inaccuracy was 0.72 mm (SD 0.40; range 0.2-1.7 mm). Inaccuracies ≥1.5 mm were observed in 2/32 cases. CONCLUSION: Our study confirms in vivo that the accuracy of the Neurolocate registration is compatible with the accuracy required for DBS procedures.

Radiosurgery for classical trigeminal neuralgia: impact of the shot size on clinical outcome.

BACKGROUND: This study compares the outcome of patients suffering from medically refractory classical trigeminal neuralgia (TN) after treatment with radiosurgery using two different shot sizes (5- and 6-mm). METHODS: All patients included in this open, prospective, non-controlled study were treated in a single institution for TN (95 cases in 93 patients) with LINear ACcelerators (LINAC) single-dose radiosurgery using a 5-mm shot (43 cases) or 6-mm shot (52 cases). The target was positioned on the intracisternal part of the trigeminal nerve. RESULTS: The mean Dmax (D0.035) to the brainstem was higher in the 6-mm group: 12.6 vs 21.3 Gy (p < 0.001). Pain relief was significantly better in the 6-mm group: at 12 and 24 months in the 6-mm group the rate of pain-free patients was 90.2 and 87.8%, respectively vs. 73.6 and 73.6% in the 5-mm group (p = 0.045). At 12 and 24 months post-radiosurgical hypoesthesia was more frequent in the 6-mm group: 47.0 and 58% vs.11.3 and 30.8% in the 5-mm group (p = 0.002). To investigate the effect of cone diameter and the dose to the brainstem on outcomes, patients were stratified into three groups: group 1 = 5-mm shot, (all Dmax < 25 Gy, 43 cases), group 2 = 6-mm shot, Dmax < 25 Gy (32 cases), group 3 = 6-mm shot Dmax > 25 Gy (20 cases). At 12 months the rates of hypoesthesia were 11.3, 33.5 and 76.0%, respectively in groups 1, 2 and 3 (p < 0.001) and the rates of recurrence of pain were 26.4, 16.5 and 5%, respectively, (p = 0.11). CONCLUSION: LINAC treatment with a 6-mm shot provided excellent control of pain, but increased the rate of trigeminal nerve dysfunction, especially when the maximum dose to the brainstem was higher than 25 Gy.

Free-water correction DTI-based tractography in brain tumor surgery: assessment with functional and electrophysiological mapping of the white matter.

Peritumoral edema prevents fiber tracking from diffusion tensor imaging (DTI). A free-water correction may overcome this drawback, as illustrated in the case of a patient undergoing awake surgery for brain metastasis. The anatomical plausibility and accuracy of tractography with and without free-water correction were assessed with functional mapping and axono-cortical evoked-potentials (ACEPs) as reference methods. The results suggest a potential synergy between corrected DTI-based tractography and ACEPs to reliably identify and preserve white matter tracts during brain tumor surgery.

Is Spinal Cord Stimulation Still Effective After One or More Surgical Revisions?

OBJECTIVES: Spinal cord stimulation (SCS) is burdened with surgical complications that may require one or several surgical revision(s), challenging its risk/benefit ratio and cost-effectiveness. Our objective was to evaluate its outcome and efficacy after one or more SCS surgical revisions. MATERIALS AND METHODS: We identified and retrospectively analyzed 116 patients treated by tonic paresthesia-based SCS who experienced one or more complication(s) requiring at least one surgical revision. Data collected included initial indication, revision indication, number of revisions, and lead design (paddle or percutaneous). Outcome after SCS revision was evaluated by pain intensity decrease (comparing baseline and postrevision Numerical Rating Scale [NRS] scores) and percentage of patients reporting pain relief ≥50%. Outcome was analyzed according to the number of surgical revisions and the revision indications. RESULTS: Most of the patients (61%) underwent only one revision (mean delay after implantation 44 months). The most frequent causes of revisions were hardware dysfunction (32%), lead migration (23%), and infection (18%). Revision(s) repaired the SCS issue in 87% of the cases. One year after the first revision, 82% of the patients reported pain relief ≥50%, and the mean NRS decrease was 4.0 compared with baseline (p < 0.001). Benefit of SCS revision tended to decrease with the number of revisions but did not differ across revision indications. No serious surgical complications related to the revision occurred, except for three hematomas occurring after repeated revisions. CONCLUSIONS: Our data suggest that surgical revision of SCS system is safe and led to significant pain relief in most of the cases, provided that the initial indication was good and that the previous stimulation was effective. However, success of SCS revision decreases with the number of revisions.

Identifying subcortical connectivity during brain tumor surgery: a multimodal study.

Bipolar direct electrical stimulation (DES) of an awake patient is the reference technique for identifying brain structures to achieve maximal safe tumor resection. Unfortunately, DES cannot be performed in all cases. Alternative surgical tools are, therefore, needed to aid identification of subcortical connectivity during brain tumor removal. In this pilot study, we sought to (i) evaluate the combined use of evoked potential (EP) and tractography for identification of white matter (WM) tracts under the functional control of DES, and (ii) provide clues to the electrophysiological effects of bipolar stimulation on neural pathways. We included 12 patients (mean age of 38.4 years) who had had a dMRI-based tractography and a functional brain mapping under awake craniotomy for brain tumor removal. Electrophysiological recordings of subcortical evoked potentials (SCEPs) were acquired during bipolar low frequency (2 Hz) stimulation of the WM functional sites identified during brain mapping. SCEPs were successfully triggered in 11 out of 12 patients. The median length of the stimulated fibers was 43.24 ± 19.55 mm, belonging to tracts of median lengths of 89.84 ± 24.65 mm. The electrophysiological (delay, amplitude, and speed of propagation) and structural (number and lengths of streamlines, and mean fractional anisotropy) measures were correlated. In our experimental conditions, SCEPs were essentially limited to a subpart of the bundles, suggesting a selectivity of action of the DES on the brain networks. Correlations between functional, structural, and electrophysiological measures portend the combined use of EPs and tractography as a potential intraoperative tool to achieve maximum safe resection in brain tumor surgery.

A New Noninvasive Frameless Registration System for Stereotactic Cranial Biopsy: A Technical Note.

BACKGROUND: Although frame-based stereotactic biopsy is still considered the gold standard for brain biopsies, frameless robot-assisted stereotactic systems are now able to provide an equal level of safety and accuracy. However, both systems suffer from a lack of efficiency of the operative workflow. OBJECTIVE: To describe the technique of a new frameless and noninvasive registration tool Neurolocate (Renishaw). This tool, combined with an intraoperative cone-beam computed tomography imaging system like O-ARM (Medtronic), might facilitate the achievement and workflow of robot-assisted stereotactic intracranial biopsies. METHODS: Neurolocate is a 3-dimensional fiducial tool fixed directly on the Neuromate (Renishaw) robot arm. It consists of 5 radio-opaque spherical fiducials, whose geometry is constant. This tool made it possible to carry out the coregistration then the biopsy in the same operating time, following a five-step procedure described here. We retrospectively extracted selected preliminary results from our initial experience. RESULTS: Over 1 year, 23 consecutive adult patients were biopsied with Neurolocate in our center. The mean overall operative time, from patient's installation to skin closure, was 97 minutes ± 27 (SD). The entire procedure took place in a single location unit (operating room), which facilitated workflow and surgical planning. No invasive gesture was performed outside of the operating time. CONCLUSION: Neurolocate is a new frameless and noninvasive registration tool that could improve workflow and flexibility for operating room management and surgical planning. It may also increase the comfort of patients undergoing robot-assisted intracranial stereotactic biopsies. The accuracy and safety profile should be addressed in specific studies.

Occipital Nerve Stimulation for Recurrent Trigeminal Neuralgia Without Occipital Pain.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe, debilitating pain condition causing physical and emotional distress. Although the management of TN is well codified with medical and then surgical treatments, 15% to 30% of patients will experience intractable pain. Neuromodulation techniques have been scarcely used for refractory TN, with only small case series and short-term follow-up. MATERIALS AND METHODS: We conducted a retrospective study of patients treated with occipital nerve stimulation (ONS) for medically and surgically resistant TN without painful trigeminal neuropathy. The effectiveness of the ONS was evaluated using the Barrow Neurological Institute (BNI) pain score and the pain relief (0%-100%) at best and at last follow-up. RESULTS: Seven patients who have refractory TN were included. The mean age at ONS was 49 years. The mean pain duration was 8.6 years. The mean number of medical and surgical treatments before ONS was six and five, respectively. A percutaneous trial was performed in five of seven patients; all responded (pain relief > 40%), and four of five patients experienced pain recurrence after explantation. Eventually, six patients had a permanent ONS implantation. The average BNI pain score before implantation was V. The mean follow-up after implantation was 59 months. All patients reported an improvement after implantation. The average BNI score and mean pain relief at best were IIIa and 86.7%, respectively. At last follow-up, the average BNI score and mean pain relief were IIIa and 58.0%, respectively, with three patients experiencing pain recurrence. Adverse events were reported for four patients who required surgical revision for lead breakage (1), erosion (1), migration (1), or hardware-related discomfort (1). One patient finally underwent explantation because of infection. CONCLUSIONS: Although ONS is not validated in this indication, these results suggest that it can induce an improvement in TN recurring after several surgical treatments, and the benefit of the stimulation can be sustained in the long term. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01842763.

Combining Awake Anesthesia with Minimal Invasive Surgery Optimizes Intraoperative Surgical Spinal Cord Stimulation Lead Placement.

Spinal cord stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in persistent spinal pain syndrome-type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that awake anesthesia (AA), consisting of target controlled intra-venous anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with minimal invasive surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily, to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or general anesthesia (MISGA group), or by laminectomy under general anesthesia (LGA group). All in all, awake surgery appears to show significantly better performance than general anesthesia in terms of patient pain coverage (65% vs. 34-62%), pain surface (50-76% vs. 50-61%) and pain intensity (65% vs. 35-40%), as well as improved secondary outcomes (quality of life, functional disability and depression). One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

Guidelines of the International Headache Society for Controlled Clinical Trials in Cluster Headache.

In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated.

Treatment of Chronic Refractory Pain by Combined Deep Brain Stimulation of the Anterior Cingulum and Sensory Thalamus (EMOPAIN Study): Rationale and Protocol of a Feasibility and Safety Study.

BACKGROUND: Deep Brain Stimulation (DBS) of the sensory thalamus has been proposed for 40 years to treat medically refractory neuropathic pain, but its efficacy remains partial and unpredictable. Recent pilot studies of DBS targeting the ACC, a brain region involved in the integration of the affective, emotional, and cognitive aspects of pain, may improve patients suffering from refractory chronic pain. ACC-DBS could be complementary to thalamic DBS to treat both the sensory-discriminative and the affective components of chronic pain, but the safety of combined DBS, especially on cognition and affects, has not been studied. METHODS: We propose a prospective, randomized, double-blind, and bicentric study to evaluate the feasibility and safety of bilateral ACC-DBS combined with unilateral thalamic DBS in adult patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. After a study period of six months, there is a cross-over randomized phase to compare the efficacy (evaluated by pain intensity and quality of life) and safety (evaluated by repeated neurological examination, psychiatric assessment, cognitive assessment, and assessment of affective functions) of combined ACC-thalamic DBS and thalamic DBS only, respectively. DISCUSSION: The EMOPAIN study will show if ACC-DBS is a safe and effective therapy for patients suffering from chronic unilateral neuropathic pain, refractory to medical treatment. The design of the study will, for the first time, assess the efficacy of ACC-DBS combined with thalamic DBS in a blinded way.

Combined thalamic and pallidal deep brain stimulation for dystonic tremor.

BACKGROUND: Deep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets. OBJECTIVES: To report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated. METHODS: Three patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition. RESULTS: The Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed. CONCLUSION: Combined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them.

Artificial intelligence to evaluate postoperative pain based on facial expression recognition.

BACKGROUND: Pain intensity evaluation by self-report is difficult and biased in non-communicating people, which may contribute to inappropriate pain management. The use of artificial intelligence (AI) to evaluate pain intensity based on automated facial expression analysis has not been evaluated in clinical conditions. METHODS: We trained and externally validated a deep-learning system (ResNet-18 convolutional neural network) to identify and classify 2810 facial expressions of 1189 patients, captured before and after surgery, according to their self-reported pain intensity using numeric rating scale (NRS, 0-10). AI performances were evaluated by accuracy (concordance between AI prediction and patient-reported pain intensity), sensitivity and specificity to diagnose pain ≥4/10 and ≥7/10. We then confronted AI performances with those of 33 nurses to evaluate pain intensity from facial expression in the same situation. RESULTS: In the external testing set (120 face images), the deep learning system was able to predict exactly the pain intensity among the 11 possible scores (0-10) in 53% of the cases with a mean error of 2.4 points. Its sensitivities to detect pain ≥4/10 and ≥7/10 were 89.7% and 77.5%, respectively. Nurses estimated the right NRS pain intensity with a mean accuracy of 14.9% and identified pain ≥4/10 and ≥7/10 with sensitivities of 44.9% and 17.0%. CONCLUSIONS: Subject to further improvement of AI performances through further training, these results suggest that AI using facial expression analysis could be used to assist physicians to evaluate pain and detect severe pain, especially in people not able to report appropriately their pain by themselves. SIGNIFICANCE: These original findings represent a major step in the development of a fully automated, rapid, standardized and objective method based on facial expression analysis to measure pain and detect severe pain.

Phantom vision after eye removal: prevalence, features and related risk factors.

AIM: Phantom eye syndrome is a poorly understood and underestimated complication of eye removal (ER). Seeing with the amputated eye, referred to as phantom vision (PV), is undoubtedly the most intriguing and confusing complication experienced by anophthalmic patients. The aim of the study was to assess PV prevalence, clinical features and risk factors after ER. METHODS: A multicentric questionnaire-based study was conducted between April 2016 and July 2017. Patients >18 years who underwent ER >3 months ago had a socket examination before inclusion. Data recorded included patients' demographics, and preoperative, surgical and postoperative features. RESULTS: One hundred patients (53 men) with a mean age of 65.1 years (29-92; SD=13.0) were included. ER indications were: uveal melanoma (n=24, 24%), trauma (n=20, 20%), retinal detachment (n=20, 20%), glaucoma (n=14, 14%) and endophthalmitis (n=12, 12%). Thirty (30%) patients experienced PV. Elementary and complex visual hallucinations were experienced by 80% and 20% of patients, respectively. PV usually appeared within the first postoperative month and tended to decrease over time. Risk factors for PV were the preoperative use of proton beam therapy (p=0.006), uveal melanoma (p=0.014), enucleation (p=0.015), anxiety with a Hospital and Anxiety Depression (HAD) score ≥8 (p=0.042), depression with a HAD score ≥8 (p=0.030), phantom eye pain (p=0.044) and phantom eye sensations (p=0.002). CONCLUSION: PV was reported by one-third of our patients. Despite being widely misunderstood, ophthalmologists and neurologists should be aware of this complication to adequately reassure patients.

Deep brain stimulation in Alzheimer's disease.

Benefits from symptomatic and etiologic treatments in Alzheimer's Disease (AD), the most frequent dementia, are still insufficient. During the last decade, several studies showed that electrical stimulation of memory circuits could enhance memory in humans without memory impairment. First, improvement of verbal recollection was reported after deep brain stimulation (DBS) of the fornix in the hypothalamus in a patient treated for morbid obesity. Several studies in epileptic patients explored by deep electrodes reported that visuo-spatial memorization was facilitated by electrical stimulation of the entorhinal cortex or theta burst stimulation of the fornix. Recent studies suggested that DBS could be useful to modulate memory circuits in patients with cognitive decline. Phase I and II studies (about 50 patients) showed that chronic fornix DBS was safe and could achieved to stabilize or slow the memory decline of some patients with mild to moderate AD, especially older ones with less severe and/or advanced disease. DBS of the cholinergic nucleus of Meynert also has been explored in phase I studies in AD and Parkinson-related dementia. Growing experimental data suggest several mechanisms of action: restoration of hippocampal theta rhythms, enhanced long term potentiation, increase of hippocampal neurogenesis, neuroprotection by release of neurotrophic factors, diffuse reactivation of hypoactive neocortical associative regions. However, DBS in AD is still investigational and numerous issues remain to be solved before envisaging its use in clinical practice, including optimal anatomical DBS target, stimulation modalities (continuous, intermittent, theta-bursts, closed loop stimulation), best candidate patients, relevant targeted symptoms, ethical considerations.

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

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.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

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

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.