A Cohort Study of CNS Tumors in Multiple Endocrine Neoplasia Type 1.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Thus, we aimed to describe the frequency, incidence, and specific clinical and histological features of central nervous system (CNS) tumors in the MEN1 population (except pituitary tumors). EXPERIMENTAL DESIGN: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed up in the French MEN1 national cohort. The standardized incidence ratio (SIR) was calculated based on the French Gironde CNS Tumor Registry. Genomic analyses were performed on somatic DNA from seven CNS tumors, including meningiomas and ependymomas from patients with MEN1, and then on 50 sporadic meningiomas and ependymomas. RESULTS: A total of 29 CNS tumors were found among the 1,498 symptomatic patients (2%; incidence = 47.4/100,000 person-years; SIR = 4.5), including 12 meningiomas (0.8%; incidence = 16.2/100,000; SIR = 2.5), 8 ependymomas (0.5%; incidence = 10.8/100,000; SIR = 17.6), 5 astrocytomas (0.3%; incidence = 6.7/100,000; SIR = 5.8), and 4 schwannomas (0.3%; incidence = 5.4/100,000; SIR = 12.7). Meningiomas in patients with MEN1 were benign, mostly meningothelial, with 11 years earlier onset compared with the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified as World Health Organization grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from patients with MEN1, whereas MEN1 deletion in one allele was present in 3/41 and 0/9 sporadic meningiomas and ependymomas, respectively. CONCLUSIONS: The incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Usefulness of thalamic beta activity for closed-loop therapy in essential tremor.

A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV2/Hz during posture/action for N = 8/10 patients; p = 0.010), 12 months after surgery (2.92 ± 1.75 at rest vs. 2.12 ± 1.78 µV2/Hz during posture/action for N = 7/10 patients; p = 0.014) and 24 months after surgery (2.32 ± 0.35 at rest vs 0.75 ± 0.78 µV2/Hz during posture/action for 4/6 patients; p = 0.017). Among the patients who exhibited a significant decrease of high-beta LFP amplitude when stimulation was Off, this phenomenon was observed at least twice during the follow-up. Although the extent of this decrease in high-beta LFPs amplitude during movements inducing tremor may vary over time, this thalamic biomarker of movement could potentially be usable for closed-loop therapy in the long term.

Evaluation of four tumour growth models to describe the natural history of meningiomas.

BACKGROUND: The incidence of newly diagnosed meningiomas, particularly those diagnosed incidentally, is continually increasing. The indication for treatment is empirical because, despite numerous studies, the natural history of these tumours remains difficult to describe and predict. METHODS: This retrospective single-centre study included 294 consecutive patients with 333 meningiomas who underwent three or more brain imaging scans. Linear, exponential, power, and Gompertz models were constructed to derive volume-time curves, by using a mixed-effect approach. The most accurate model was used to analyse tumour growth and predictors of rapid growth. FINDINGS: The Gompertz model provided the best results. Hierarchical clustering at the time of diagnosis and at the end of follow-up revealed at least three distinct groups, which can be described as pseudoexponential, linear, and slowing growth with respect to their parameters. Younger patients and smaller tumours were more frequent in the pseudo-exponential clusters. We found that the more "aggressive" the cluster, the higher the proportion of patients with grade II meningiomas and who have had a cranial radiotherapy. Over a mean observation period of 56.5 months, 21% of the tumours moved to a cluster with a lower growth rate, consistent with the Gompertz's law. INTERPRETATION: Meningiomas exhibit multiple growth phases, as described by the Gompertz model. The management of meningiomas should be discussed according to the growth phase, comorbidities, tumour location, size, and growth rate. Further research is needed to evaluate the associations between radiomics features and the growth phases of meningiomas. FUNDING: No funding.

Descriptive Epidemiology of Ependymal Tumors in Gironde, France: Results from the Gironde Registry for the 2000-2018 Period.

BACKGROUND: The Gironde Central Nervous System (CNS) Tumor Registry, in collaboration with the French National Cancer Institute, is the largest population-based registry focused exclusively on primary CNS tumors in France and represents a population of 1.62 million. This report focuses on ependymal tumors to refine current knowledge and provide up-to-date data on the epidemiology of these rare tumors. MATERIAL AND METHODS: All of the ependymal tumors were extracted from the Gironde CNS Tumor Registry for the years 2000-2018. Demographic and clinical characteristics, incidence rates, and time trends as well as survival outcomes were analyzed. RESULTS: One hundred forty-four ependymal tumors were retrieved, which represented 2.3% of all the CNS tumors recorded in the same period. Histological subtype was significantly dependent on age and topography in the CNS. The median age at diagnosis was 46 years. The annual incidence rates varied between 0.15/100,000 (2004) and 0.96/100,000 (2016), with a significant increase over the study period by 4.67% per year. Five-year and 10-year OS rates were 87% and 80%, respectively. CONCLUSION: An increase in the incidence of ependymal tumors was observed over the past two decades. Further studies are needed to confirm this result and provide etiological clues.

A case series of percutaneous transforamen ovale biopsies in cavernous sinus lesions.

BACKGROUND: The majority of cavernous sinus lesions are meningiomas, for which treatment (fractioned radiotherapy or radiosurgery), if indicated, is usually initiated upon image-based diagnosis. However, this region can be affected by a wide variety of pathological processes and the risk of misdiagnosis exists. As pathological diagnosis can be obtained by biopsy through the foramen ovale in selected cases, we asked the question as to whether systematically performing this procedure before treatment would provide additional, relevant diagnostic information. METHODS: All the cases referred to our department between January 2008 and December 2019 for cavernous sinus lesions that were considered for treatment and anatomically suitable for transforamen ovale biopsy were included. Outcomes and subsequent treatment or follow-up data were collected. RESULTS: Thirty-five patients were included. Twenty-six were highly suspected to have meningioma or schwannoma at imaging, among whom biopsy allowed diagnosis confirmation in 17 cases (65%). For the nine patients for whom biopsy was indicated upon suspected malignancy or inflammatory disease on imaging, biopsy revealed three meningiomas and one lymphoma and was not contributory in five cases (56%), three of which underwent open surgery. Three patients (8.5%) had persistent neuralgia at the last follow-up. CONCLUSIONS: When cavernous sinus meningioma or schwannoma is highly suspected upon predefined imaging criteria by an experienced neuroradiologist, invasive exploration before treatment does not seem to be indicated. Otherwise, transforamen ovale biopsy might be consider in selected cases as a minimally invasive option to obtain pathological analysis.

Prediction of Clinical Deep Brain Stimulation Target for Essential Tremor From 1.5 Tesla MRI Anatomical Landmarks.

Background: Deep brain stimulation is an efficacious treatment for refractory essential tremor, though targeting the intra-thalamic nuclei remains challenging. Objectives: We sought to develop an inverse approach to retrieve the position of the leads in a cohort of patients operated on with optimal clinical outcomes from anatomical landmarks identifiable by 1.5 Tesla magnetic resonance imaging. Methods: The learning database included clinical outcomes and post-operative imaging from which the coordinates of the active contacts and those of anatomical landmarks were extracted. We used machine learning regression methods to build three different prediction models. External validation was performed according to a leave-one-out cross-validation. Results: Fifteen patients (29 leads) were included, with a median tremor improvement of 72% on the Fahn-Tolosa-Marin scale. Kernel ridge regression, deep neural networks, and support vector regression (SVR) were used. SVR gave the best results with a mean error of 1.33 ± 1.64 mm between the predicted target and the active contact position. Conclusion: We report an original method for the targeting in deep brain stimulation for essential tremor based on patients' radio-anatomical features. This approach will be tested in a prospective clinical trial.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

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.

Persistent Trigeminal Artery as Collateral Circulation in Ischemic Stroke.

The persistent trigeminal artery is the most frequent of the persistent embryonic carotid-basilar artery anastomoses. In the literature, it has most often been described in relation to cerebrovascular pathologies such as aneurysms, vascular nerve compression, trigeminal cavernous fistulas, and thromboembolic ischemia. Its role as collateral circulation, thus supplying brain perfusion during main arterial trunk occlusion, has seldom been described. We describe the case of a patient who presented with a stroke due to a traumatic dissection of the internal carotid artery at the neck, in which the infarction may have been limited by a persistent trigeminal artery.

Surgical Site Infections after glioblastoma surgery: results of a multicentric retrospective study.

BACKGROUND: The effects of surgical site infections (SSI) after glioblastoma surgery on patient outcomes are understudied. The aim of this retrospective multicenter study was to evaluate the impact of SSI on the survival of glioblastoma patients. METHODS: Data from SSI cases after glioblastoma surgeries between 2009 and 2016 were collected from 14 French neurosurgical centers. Collected data included patient demographics, previous medical history, risk factors, details of the surgical procedure, radiotherapy/chemotherapy, infection characteristics, and infection management. Similar data were collected from gender- and age-paired control individuals. RESULTS: We used the medical records of 77 SSI patients and 58 control individuals. 13 were excluded. Our analyses included data from 64 SSI cases and 58 non-infected glioblastoma patients. Infections occurred after surgery for primary tumors in 38 cases (group I) and after surgery for a recurrent tumor in 26 cases (group II). Median survival was 381, 633, and 547 days in patients of group I, group II, and the control group, respectively. Patients in group I had significantly shorter survival compared to the other two groups (p < 0.05). The one-year survival rate of patients who developed infections after surgery for primary tumors was 50%. Additionally, we found that SSIs led to postoperative treatment discontinuation in 30% of the patients. DISCUSSION: Our findings highlighted the severity of SSIs after glioblastoma surgery, as they significantly affect patient survival. The establishment of preventive measures, as well as guidelines for the management of SSIs, is of high clinical importance.

Spatial mechanistic modeling for prediction of the growth of asymptomatic meningiomas.

BACKGROUND AND OBJECTIVE: Mathematical modeling of tumor growth draws interest from the medical community as they have the potential to improve patients' care and the use of public health resources. The main objectives of this work are to model the growth of meningiomas - slow-growing benign tumors requiring extended imaging follow-up - and to predict tumor volume and shape at a later desired time using only two times examinations. METHODS: We develop two variants of a 3D partial differential system of equations (PDE) which yield after a spatial integration systems of ordinary differential equations (ODE) that relate tumor volume with time. Estimation of models parameters is a crucial step to obtain a personalized model for a patient that can be used for descriptive or predictive purposes. As PDE and ODE systems share the same parameters, they are both estimated by fitting the ODE systems to the tumor volumes obtained from MRI examinations acquired at different times. A population approach allows to compensate for sparse sampling times and measurement uncertainties by constraining the variability of the parameters in the population. RESULTS: Description capabilities of the models are investigated in 39 patients with benign asymptomatic meningiomas who had had at least three surveillance MRI examinations. The two models can fit to the data accurately and more realistically than a naive linear regression. Prediction performances are validated for 33 patients using a population approach. Mean relative errors in volume predictions are less than 10% with ODE systems versus 12.5% with the naive linear model using only two times examinations. Concerning the shape, the mean Sørensen-Dice coefficients are 85% with the PDE systems in a subset of 10 representative patients. CONCLUSIONS: Our strategy - based on personalization of mathematical model - provides a good insight on meningioma growth and may help decide whether to extend the follow-up or to treat the tumor.

A Phase 2 Randomized Trial of Asleep versus Awake Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: Asleep deep brain stimulation (DBS) for Parkinson's disease (PD) is being performed more frequently; however, motor outcomes and safety of asleep DBS have never been assessed in a prospective randomized trial. METHODS: We conducted a prospective, randomized, noncomparative trial to assess the motor outcomes of asleep DBS. Leads were implanted in the subthalamic nucleus (STN) according to probabilistic stereotactic coordinates with a surgical robot under O-arm© imaging guidance under either general anesthesia without microelectrode recordings (MER) (20 patients, asleep group) or local anesthesia with MER and clinical testing (9 patients, awake group). RESULTS: The mean motor improvement rates on the Unified Parkinson's Disease Rating Scale Part III (UPDRS-3) between OFF and ON stimulation without medication were 52.3% (95% CI: 45.4-59.2%) in the asleep group and 47.0% (95% CI: 23.8-70.2%) in the awake group, 6 months after surgery. Except for a subcutaneous hematoma, we did not observe any complications related to the surgery. Three patients (33%) in the awake group and 8 in the asleep group (40%) had at least one side effect potentially linked with neurostimulation. CONCLUSIONS: Owing to its randomized design, our study supports the hypothesis that motor outcomes after asleep STN-DBS in PD may be noninferior to the standard awake procedure.

Increased Incidence of Intracranial Meningiomas in Patients With Acromegaly.

BACKGROUND: An increased incidence of various neoplasms has been described in patients with acromegaly, and there is evidence to suggest that growth factors are risk factors for the development of meningiomas. OBJECTIVE: To study if patients with acromegaly are more at risk for developing intracranial meningiomas. METHODS: We conducted an observational study on 221 consecutive acromegalic patients recruited between January 1, 2000 and December 31, 2015, and 357 consecutive patients with a nonsomatotropic pituitary adenoma recruited between March 1, 2015 and December 31, 2016, in our institution. Patients underwent a gadolinium-enhanced 3D T1 brain magnetic resonance imaging to look for meningiomas. The proportion of meningiomas was compared between the 2 groups, and the standardized incidence ratio (SIR) was computed from the incidence rates of meningiomas observed in the population of acromegalic patients and compared to that of the general population given by the local registry of central nervous system tumors. RESULTS: Patients with acromegaly had a significant risk for developing intracranial meningiomas as compared to patients without acromegaly (7.7% vs 2.2%, P = .005, OR = 3.45 [1.46; 8.15]). There was a significant increased incidence of intracranial meningiomas in patients with acromegaly (SIR = 126 [25; 367]) as compared to the general population. CONCLUSION: Our study suggests strongly that patients with acromegaly are more at risk for developing intracranial meningiomas.

Localization of Deep Brain Stimulation Electrode by Image Registration Is Software Dependent: A Comparative Study between Four Widely Used Software Programs.

BACKGROUND: The control of the anatomic position of the active contacts is essential to understand the effects and adapt the settings of the neurostimulation. The localization is commonly assessed by a registration between the preoperative MRI and the postoperative CT scan. However, its accuracy depends on the quality of the registration algorithm and many software programs are available. OBJECTIVE: To compare the localization of implanted deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) between four registration devices. METHODS: The preoperative stereotactic MRI was co-registered and fused with the 3-month postoperative CT scan in 27 patients implanted in the STN for Parkinson's disease (53 leads). Localizations of the active contacts were calculated in the stereotactic frame space and compared between software programs. RESULTS: The coordinates of the active contacts were different between software programs in the 3 axes (p < 0.001) with a mean vectorial error between the deepest contact locations of 1.17 mm (95% CI 1.09-1.25). CONCLUSION: We found a small but significant difference in the coordinates calculated on four different devices. These results have to be considered when performing studies comparing active contact locations or when following patients with an implanted DBS lead.

Contralateral Transcranial Approach to Tuberculum Sellae Meningiomas: Long-Term Visual Outcomes and Recurrence Rates.

BACKGROUND: One of the most challenging aspects of the surgical treatment of tuberculum sellae meningioma is to control the involvement of the inferomedial side of the optic nerve, which is not directly visualized by an ipsilateral approach and thus requires optic nerve mobilization. METHODS: Between 2003 and 2017, 21 consecutive patients were operated on using this approach. The surgical technique is described and the visual outcomes, resection and recurrence rates, and complications are analyzed. RESULTS: Twenty patients were included, with a median follow-up of 5.6 years. Regarding visual outcomes, among the 19 patients who had a visual impairment before surgery, 14 (74%) improved, 2 were stabilized (10%), and 2 (10%) showed a worsening of the most-compromised optic nerve and 1 (5%) of the less-compromised optic nerve. Gross total resection was achieved in 18 patients (90%) and 1 patient experienced recurrence 10 years after the initial surgery. CONCLUSIONS: This approach allowed lower mobilization of the compromised optic nerve, better preservation of the vascularization of the visual pathways, and direct access to the inferomedial side of the optic nerve.

Anterior cervical intradural arachnoid cyst, a rare cause of spinal cord compression: a case report with video systematic literature review.

PURPOSE: Mostly seen at the thoracic level, arachnoid cysts are a very rare cause of cervical spinal cord compression. Generally treated by laminectomy and cyst fenestration, this approach does not allow removing the cyst in its entirety without manipulating the weakened spinal cord. The aim of this report is to present the case of a cervical intradural arachnoid cyst surgically removed by an anterior approach with corporectomy. METHODS: Here is the case of an 18-year-old amateur boxer presenting with a voluminous cervical intradural anterior arachnoid cyst, extending from C2 to C5. Symptoms were cervical pain, quadriparesis, and clumsiness of both arms which had appeared just after a traffic accident. An anterior approach was chosen, through a C5 corporectomy. RESULTS: The patient totally recovered from his sensitive symptoms at discharge and from his motor symptoms 6 weeks later. Early as well as 3-years post-operatively, MRI confirmed expansion of the spinal cord without any centro-medullar signal. The patient remained asymptomatic 3 years after surgery. Since the first report in 1974, 16 cases of symptomatic cervical intradural arachnoid cysts were treated via a posterior approach, one by MRI-guided biopsy, and one was re-operated on through an anterior approach. For 14 patients, their conditions had improved, while one died of pneumonia, one presented a condition worsened, and one had a stable neurological status. CONCLUSION: Using an anterior approach is a safe procedure that allows resection of a cervical arachnoid cyst without any manipulation of the weakened spinal cord, while giving the best possible view.

Oculomotor nerve palsy induced by internal carotid artery aneurysm: prognostic factors for recovery.

BACKGROUND: Aneurysms at the posterior face of the internal carotid artery can lead to oculomotor nerve palsy (ONP) with an uncertain prognosis of recovery post-treatment. The aim of this study was to define the prognostic factors for ONP recovery, with particular interest in treatment modality (surgery or endovascular techniques). METHOD: A literature review was performed to select the most pertinent prognostic factors. A retrospective study was then performed to determine whether these factors had significantly modified the prognosis of ONP recovery in our series of patients. RESULTS: In the literature, factors linked to poorer outcome were age, vascular risk factors, initial ONP severity and delay before treatment; better recovery was associated with surgical treatment. Between 2000 and 2013, 23 consecutive patients were treated in our department for ONP-inducing aneurysms: 14 by endovascular embolization and 9 by surgical clipping and aneurysm puncture. Mean follow-up was 48.8 months. After treatment, overall recovery occurred in 87% of cases, always within 6 months. Apart from treatment modality, no selected prognostic factor significantly modified the quality or timing of ONP recovery. In the endovascular group, four patients recovered completely, seven partially and three did not recover. In the surgical group, seven patients recovered completely and two partially. Surgery was significantly associated with a more complete and earlier ONP recovery (p < 0.05). CONCLUSIONS: Surgery was associated with a more complete and earlier ONP recovery as compared to endovascular treatment, confirming the results of previous studies. However, conclusions must be confirmed by a prospective randomized study.

Effect of chronic cortical stimulation on chronic severe tinnitus: a prospective randomized double-blind cross-over trial and long-term follow up.

BACKGROUND: Chronic severe tinnitus can be greatly detrimental to quality of life. Some authors have reported benefit of repetitive transcranial magnetic stimulation, others of electrical cortical stimulation by stimulating the Heschl's gyrus or secondary auditory areas. OBJECTIVE: To evaluate the efficacy of chronic electrical epidural stimulation of the auditory cortex on severe and disabling tinnitus. METHOD: In this double-blind randomized cross-over, patients with chronic (at least 2 years), severe (Strukturierte Tinnitus-Interview, STI score > 19), unilateral or strongly lateralized tinnitus were included. After open-phase stimulation for 4 months, patients were randomized into 2 groups for double-blind stimulation with cross-over between significant and non-significant phases and wash-out in between. Each of the 3 phases was 2 weeks in duration. Patients were chronically stimulated and followed if not explanted. A decrease of STI score >35% was considered as clinically significant. RESULTS: None of the 9 patients included achieved significant improvement during the double-blind phase. Four were explanted, 2 owing to lack of effect, one for breast cancer under the stimulator, and another for psychiatric decompensation. Five are still stimulated. Three felt slight to great subjective effectiveness, the remaining 2 reported benefits and still requested stimulation. CONCLUSIONS: This study did not find an objective efficiency of chronic cortical stimulation for severe and resistant tinnitus. The discordance between the results in double-blind and open evaluations could be related to a placebo effect of surgery, but may also be explained by a poorly defined target, a too short randomized phase, or inappropriate outcome measures. Clinical trial reference: NCT00486577.