Surgical management of large lower cranial nerves schwannomas: long term results of a less aggressive resection strategy.

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Single-fraction radiosurgery outcomes for large vestibular schwannomas in the upfront or post-surgical setting: a systematic review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines.

PURPOSE: To perform a systematic review of literature specific to single-fraction stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS), maximum diameter ≥ 2.5 cm and/or classified as Koos Grade IV, and to present consensus recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. We considered eligible prospective and retrospective studies, written in the English language, reporting treatment outcomes for large VS; SRS for large post-operative tumors were analyzed in aggregate and separately. RESULTS: 19 of the 229 studies initially identified met the final inclusion criteria. Overall crude rate of tumor control was 89% (93.7% with no prior surgery vs 87.7% with prior surgery). Rates of salvage microsurgical resection, need for shunt, and additional SRS in all series versus those with no prior surgery were 9.6% vs 3.3%, 4.7% vs 6.4% and 1% vs 0.9%, respectively. Rates of facial palsy and hearing preservation in all series versus those with no prior surgery were 1.3% vs 3.4% and 34.2% vs 40.4%, respectively. CONCLUSIONS: Upfront SRS resulted in high rates of tumor control with acceptable rates of facial palsy and hearing preservation as compared to the results in those series including patients with prior surgery (level C evidence). Therefore, although large VS are considered classic indication for microsurgical resection, upfront SRS can be considered in selected patients and we recommend a prescribed marginal dose from 11 to 13 Gy (level C evidence).

Assessing Tumor Volume for Sporadic Vestibular Schwannomas: A Comparison of Methods of Volumetry.

INTRODUCTION: The size of vestibular schwannomas (VS) is a major factor guiding the initial decision of treatment and the definition of tumor control or failure. Accurate measurement and standardized definition are mandatory; yet no standard exist. Various approximation methods using linear measures or segmental volumetry have been reported. We reviewed different methods of volumetry and evaluated their correlation and agreement using our own historical cohort. METHODS: We selected patients treated for sporadic VS by Gammaknife radiosurgery (GKRS) in our department. Using the stereotactic 3D T1 enhancing MRI on the day of GKRS, 4 methods of volumetry using linear measurements (5-axis, 3-axis, 3-axis-averaged, and 1-axis) and segmental volumetry were compared to each other. The degree of correlation was evaluated using an intraclass correlation test (ICC 3,1). The agreement between the different methods was evaluated using Bland-Altman diagrams. RESULTS: A total of 2,188 patients were included. We observed an excellent ICC between 5-axis volumetry (0.98), 3-axis volumetry (0.96), and 3-axis-averaged volumetry (0.96) and segmental volumetry, respectively, irrespective of the Koos grade or Ohata classification. The ICC for 1-axis volumetry was lower (0.72) and varied depending on the Koos and Ohata subgroups. None of these methods were substitutable. CONCLUSION: Although segmental volumetry is deemed the most accurate method, it takes more effort and requires sophisticated computation systems compared to methods of volumetry using linear measurements. 5-axis volumetry affords the best adequacy with segmental volumetry among all methods under assessment, irrespective of the shape of the tumor. 1-axis volumetry should not be used.

Stereotactic Therapies for Meningiomas.

Although surgery remains the mainstay of treatment for most meningiomas, radiotherapy, specifically stereotactic radiosurgery, has become more commonplace as first-line therapy for select meningioma cases, particularly small meningiomas in challenging or high-risk anatomic locations. Radiosurgery for specific groups of meningiomas have been found to provide local control rates comparable to surgery alone. In this chapter stereotactic techniques for the treatment of meningiomas such as stereotactic radiosurgery by using Gamma knife or Linear Accelerator-based techniques (modified LINAC, Cyberknife, etc.) as well as stereotactically guided implantation or radioactive seeds for brachytherapy are introduced.

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.

Deep Brain Stimulation-Withdrawal Syndrome in Parkinson's Disease: Risk Factors and Pathophysiological Hypotheses of a Life-Threatening Emergency.

BACKGROUND AND OBJECTIVES: Subthalamic nucleus deep brain stimulation (DBS) is the most common therapeutic surgical procedure for patients with Parkinson's disease with motor fluctuations, dyskinesia, or tremor. Routine follow-up of patients allows clinicians to anticipate replacement of the DBS battery reaching the end of its life. Patients who experience a sudden stop of the DBS battery experience a rapid worsening of symptoms unresponsive to high dose of levodopa, in a life-threatening phenomenon called "DBS-withdrawal syndrome." In the current context of the COVID-19 pandemic, in which many surgeries are being deprogrammed, it is of utmost importance to determine to what extent DBS battery replacement surgeries should be considered an emergency. In this study, we attempt to identify risk factors of DBS-withdrawal syndrome and provide new insights about pathophysiological hypotheses. We then elaborate on the optimal approach to avoid and manage such a situation. MATERIALS AND METHODS: We conducted a systematic review of the literature on the subject and reported the cases of 20 patients (including five from our experience) with DBS-withdrawal syndrome, comparing them with 15 undisturbed patients (including three from our experience), all having undergone neurostimulation discontinuation. RESULTS: A long disease duration at battery removal and many years of DBS therapy are the main potential identified risk factors (p < 0.005). In addition, a trend for older age at the event and higher Unified Parkinson's Disease Rating Scale motor score before initial DBS implantation (evaluated in OFF-drug condition) was found (p < 0.05). We discuss several hypotheses that might explain this phenomenon, including discontinued functioning of the thalamic-basal ganglia loop due to DBS-stimulation cessation in a context in which cortical-basal ganglia loop had lost its cortical input, and possible onset of a severe bradykinesia through the simultaneous occurrence of an alpha and high-beta synchronized state. CONCLUSIONS: The patients' clinical condition may deteriorate rapidly, be unresponsive to high dose of levodopa, and become life-threatening. Hospitalization is suggested for clinical monitoring. In the context of the current COVID-19 pandemic, it is important to widely communicate the replacement of DBS batteries reaching the end of their life. More importantly, in cases in which the battery has stopped, there should be no delay in performing replacement as an emergent surgery.

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

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.

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

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.

Is Real-Time Inverse Planning Optimizing Dose to the Normal Brain? A Prospective Comparative Trial in a Series of Brain Metastases Treated by Stereotactic Radiosurgery.

BACKGROUND: Radiosurgery has demonstrated good safety and efficacy in the treatment of multiple brain metastases (BMs). However, multi-target dose planning can be challenging and time-consuming. A recently developed real-time inverse treatment planning (IP) by convex optimization has been demonstrated to produce high-quality treatment plans with good conformity and selectivity in single-target plans. We intended to test the capacity of this IP to rapidly generate efficient plans while optimizing the preservation of normal tissue in multiple BM. METHODS: Seventy-nine patients (mean age 62.4, age range 22-85) with a total of 272 BMs were treated by Gamma Knife Radiosurgery. All subjects were treated using a forward planning (FP) technique by an expert neurosurgeon. The new Intuitive Plan was applied and able to automatically generate an alternative plan for each patient. All planning variables were collected from the IP to be compared with the corresponding measurements obtained from the FP. A paired sample t test was applied to compare the 2 plans for the following variables: brain volumes receiving 10 Gy (V10) (primary endpoint), and 12 Gy (V12), planning indices (selectivity, coverage, gradient, and Paddick Conformity Index [PCI]), beam-on time (BOT), and integral doses. Additionally, the noninferiority margin for each item was calculated, and the 2 plans were compared for noninferiority using a paired t test. RESULTS: The mean age of patients was 62.4 years old (age range 22-85), with a sex ratio of 1.02. The average number of lesions per patient was 3.4 (range 1-12). The mean prescription dose was 21.46 Gy (range 14-24 Gy). Noninferiority of the IP was concluded for V10, V12, prescription isodose volume, BOT, PCI, and selectivity. The V10 (and V12) was significantly lower with the IP (p < 0.001). These volumes were 8.69 cm3 ± 11.39 and 5.47 cm3 ± 7.03, respectively, for the FP and 7.57 cm3 ± 9.44 and 4.78 cm3 ± 5.86 for the IP. Only the coverage was significantly lower with the IP (-2.3%, p < 0.001), but both selectivity (+17%) and PCI (+15%) were significantly higher with the IP than FP (p < 0.001). CONCLUSION: This IP demonstrated its capacity to generate multi-target plans rapidly, with a dose to the brain (V10) and BOT noninferior to the one of a human expert planner. These results would benefit from confirmation in a larger prospective series.

Mask-Based versus Frame-Based Gamma Knife ICON Radiosurgery in Brain Metastases: A Prospective Randomized Trial.

BACKGROUND: Radiosurgery is performed with a diversity of instruments relying usually either on a stereotactic frame or a mask for patient head fixation. Comfort and safety efficacy of the 2 systems have never been rigorously evaluated and compared. MATERIAL AND METHOD: Between February 2016 and January 2017, 58 patients presenting with nonsmall cell lung cancer brain metastases have been treated by Gamma Knife radiosurgery (GKS) with random use of a frame or a mask for fixation were included patients older than 18, with <5 brain metastases (at the exclusion of brainstem and optic pathway's locations) and no earlier history of radiotherapy. The primary outcome measure was the pain scale assessment (PSA) at the beginning of the GKS procedure. RESULTS: The PSA at the beginning of the GKS procedure was not different between the 2 groups. The PSA at the day before GKS, before magnetic resonance imaging, just after frame application, and the day after radiosurgery (departure) has shown no difference between the 2 groups. At the end of the radiosurgery itself (just after frame or mask removal) and 1 h after, the mean pain scale was higher in patients treated with the frame (p < 0.05 and p < 0.001, respectively) but 2 patients were not able to tolerate the mask discomfort and had to be treated with frame. Tumor control and morbidity probability were demonstrated to be no difference between the 2 groups in this population of patients with BM not in highly functional area. The median of the extra dose to the body due to the cone-beam computed tomography was 7.5 mGy with a maximum of 35 mGy in patients treated with a mask fixation (null in the others treated with frame). Mask fixation was associated to longer treatment time although the beam on time was not different between the 2 groups. CONCLUSION: In selected patients, with brain oligo-metastases out of critical location, single-dose mask-based GKS can be done with a comfort and a safety efficacy comparable to frame-based GKS. There seems to be no clear patient data that confirm the value of the mask system with regards to comfort.

Is salvage surgery for large vestibular schwannomas after failed gamma knife radiosurgery more challenging?

In order to verify whether a previous gamma knife surgery (GKS) treatment could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we have compared group of patients operated on for large VS after failed GKS to a group of genuine VS that underwent the same functional nerve-sparing resection technique regimen in the same period. Single center retrospective cohort study of 23 consecutive GKS failure and 170 genuine VS patients operated on between April 2003 and March 2019. After resection, patients were allocated to a Wait-&-rescan or an upfront GKS policy. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 95% of the GKS failure and 84% of the genuine VS patients (p = .25). The median volume of tumor residue was .56 cc in the GKS failure group and .62 cc in the genuine VS group (p = .70). Tumor control was achieved in 91% and 83% of cases with a mean follow-up of 74 and 63 months in the GKS failure and the genuine VS populations, respectively. The 1-, 5-, and 7-year progression-free survival were 100%, 95%, and 85% respectively in the GKS failure group and 97%, 80%, and 81% in the genuine VS group (p = .27). Despite significant modifications of the microsurgical environment associated to salvage surgery after GKS failure, a functional nerve-sparing resection is an effective strategy to optimize the results on facial nerve function, with similar long-term tumor control to those observed in the genuine VS population.

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

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.

ESSFN Conference Proceedings, Marseille, France, September 8-11, 2021.

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

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.

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

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.

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

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.

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

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%, I2 = 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%, I2 = 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%, I2 = 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%, I2 = 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.

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.

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 ¼ 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 ¼, 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.

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.