Tumor control and radiobiological fingerprint after Gamma Knife radiosurgery for posterior fossa meningiomas: A series of 46 consecutive cases.

Gamma Knife radiosurgery (GKR) can be a valuable treatment option for posterior cranial fossa meningiomas (PCFM). We retrospectively analyzed outcomes of GKR for PCFM. Were included forty-six patients with 47 PCFM. Primary endpoint was tumor control. Secondary endpoint was clinical improvement. Biologically effective dose (BED) was evaluated in relationship to primary and secondary outcomes. Mean marginal dose was 12.4 Gy (median 12, 12-14). Mean BED was 63.6 Gy (median 65, 49.1-88.3). Mean target volume (TV) was 2.21 cc (range 0.3-8.9 cc). Overall tumor control rate was 93.6% (44/47) after mean follow-up of 47.8 months ± 28.46 months (median 45.5, range 6-108). Radiological progression-free survival at 5 years was 94%. Higher pretherapeutic TVs were predictive for higher likelihood of tumor progression (Odds ratio, OR 1.448, 95% confidence interval - CI 1.001-2.093, p = 0.049). At last clinical follow-up, 28 patients (71.8%) remained stable, 10 (25.6%) improved and 1 patient (2.6%) worsened. Using logistic regression, the relationship between BED and clinical improvement was assessed (OR 0.903, standard error 0.59, coefficient 0.79-1.027, CI -0.10; 0.01; p = 0.14). The highest probability of clinical improvement corresponded to a range of BED values between 56 and 61 Gy. Primary GKR for PCFM is safe and effective. Higher pretherapeutic TV was predictor of volumetric progression. Highest probability of clinical improvement might correspond to a range of BED values between 56 and 61 Gy, although this was not statistically significant. The importance of BED should be further validated in larger cohorts, other anatomical locations and other pathologies

Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas.

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1-73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3-9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications

Radiosurgery for Benign Vertebral Body Hemangiomas of the Spine: A Systematic Review and Meta-Analysis.

Spinal vertebral hemangiomas (SVHs) are the most common benign tumors of the spine. We performed a systematic review and meta-analysis of radiosurgery (RS) for SVHs. We reviewed articles published between January 1990 and December 2020 on PubMed. Tumor control, pain relief, and damage to surrounding tissues were evaluated with separate meta-analyses. This study was performed in accordance with the published Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 23 patients with 24 SVHs were reported in 3 studies. Follow-up time was 7.3-84 months. The vast majority of lesions were located at dorsal level (n = 18; 75%). In 20 (83.3%) patients, pain was the initial clinical presentation. Complete, partial, and stable responses after radiation were reported in 45.7% (P < 0.001), 23.6% (P = 0.02), and 37.2% (P = 0.7) of cases. Overall response was reported in 94.1% (P = 0.7). No progressive disease was reported. Pain relief was achieved in 87.5% of patients (P = 0.2). Damage to surrounding tissue caused by irradiation was reported in 22.3% (P = 0.02) of cases in 1 study, in which higher doses of radiation were delivered. Radiosurgery is safe and effective for SVHs. Pain relief after RS in symptomatic patients was extremely high, while no progressive disease was reported. Damage to surrounding tissues was reported in only 1 series and included osteitis, osteonecrosis, or soft tissue injury after higher radiation doses

Preserving normal facial nerve function and improving hearing outcome in large vestibular schwannomas with a combined approach: planned subtotal resection followed by gamma knife radiosurgery.

To perform planned subtotal resection followed by gamma knife surgery (GKRS) in a series of patients with large vestibular schwannoma (VS), aiming at an optimal functional outcome for facial and cochlear nerves. Patient characteristics, surgical and dosimetric features, and outcome were collected prospectively at the time of treatment and during the follow-up. A consecutive series of 32 patients was treated between July 2010 and June 2016. Mean follow-up after surgery was 29 months (median 24, range 4-78). Mean presurgical tumor volume was 12.5 cm3 (range 1.47-34.9). Postoperative status showed normal facial nerve function (House-Brackmann I) in all patients. In a subgroup of 17 patients with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 16 (94.1%) retained serviceable hearing. Among them, 13 had normal hearing (Gardner-Robertson class 1) before surgery, and 10 (76.9%) retained normal hearing after surgery. Mean duration between surgery and GKRS was 6.3 months (range 3.8-13.9). Mean tumor volume at GKRS was 3.5 cm3 (range 0.5-12.8), corresponding to mean residual volume of 29.4% (range 6-46.7) of the preoperative volume. Mean marginal dose was 12 Gy (range 11-12). Mean follow-up after GKRS was 24 months (range 3-60). Following GKRS, there were no new neurological deficits, with facial and hearing functions remaining identical to those after surgery in all patients. Three patients presented with continuous growth after GKRS, were considered failures, and benefited from the same combined approach a second time. Our data suggest that large VS management, with planned subtotal resection followed by GKRS, might yield an excellent clinical outcome, allowing the normal facial nerve and a high level of cochlear nerve functions to be retained. Our functional results with this approach in large VS are comparable with those obtained with GKRS alone in small- and medium-sized VS. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control

Graph Theoretical Analysis of Structural Covariance Reveals the Relevance of Visuospatial and Attentional Areas in Essential Tremor Recovery After Stereotactic Radiosurgical Thalamotomy.

Essential tremor (ET) is the most common movement disorder. Its pathophysiology is only partially understood. Here, we leveraged graph theoretical analysis on structural covariance patterns quantified from morphometric estimates for cortical thickness, surface area, and mean curvature in patients with ET before and one year after (to account for delayed clinical effect) ventro-intermediate nucleus (Vim) stereotactic radiosurgical thalamotomy. We further contrasted the observed patterns with those from matched healthy controls (HCs). Significant group differences at the level of individual morphometric properties were specific to mean curvature and the post-/pre-thalamotomy contrast, evidencing brain plasticity at the level of the targeted left thalamus, and of low-level visual, high-level visuospatial and attentional areas implicated in the dorsal visual stream. The introduction of cross-correlational analysis across pairs of morphometric properties strengthened the presence of dorsal visual stream readjustments following thalamotomy, as cortical thickness in the right lingual gyrus, bilateral rostral middle frontal gyrus, and left pre-central gyrus was interrelated with mean curvature in the rest of the brain. Overall, our results position mean curvature as the most relevant morphometric feature to understand brain plasticity in drug-resistant ET patients following Vim thalamotomy. They also highlight the importance of examining not only individual features, but also their interactions, to gain insight into the routes of recovery following intervention

Impact of combined use of intraoperative MRI and awake microsurgical resection on patients with gliomas: a systematic review and meta-analysis.

Microsurgical resection of primary brain tumors located within or near eloquent areas is challenging. Primary aim is to preserve neurological function, while maximizing the extent of resection (EOR), to optimize long-term neurooncological outcomes and quality of life. Here, we review the combined integration of awake craniotomy and intraoperative MRI (IoMRI) for primary brain tumors, due to their multiple challenges. A systematic review of the literature was performed, in accordance with the Prisma guidelines. Were included 13 series and a total number of 527 patients, who underwent 541 surgeries. We paid particular attention to operative time, rate of intraoperative seizures, rate of initial complete resection at the time of first IoMRI, the final complete gross total resection (GTR, complete radiological resection rates), and the immediate and definitive postoperative neurological complications. The mean duration of surgery was 6.3 h (median 7.05, range 3.8-7.9). The intraoperative seizure rate was 3.7% (range 1.4-6; I^2 = 0%, P heterogeneity = 0.569, standard error = 0.012, p = 0.002). The intraoperative complete resection rate at the time of first IoMRI was 35.2% (range 25.7-44.7; I^2 = 66.73%, P heterogeneity = 0.004, standard error = 0.048, p < 0.001). The rate of patients who underwent supplementary resection after one or several IoMRI was 46% (range 39.8-52.2; I^2 = 8.49%, P heterogeneity = 0.364, standard error = 0.032, p < 0.001). The GTR rate at discharge was 56.3% (range 47.5-65.1; I^2 = 60.19%, P heterogeneity = 0.01, standard error = 0.045, p < 0.001). The rate of immediate postoperative complications was 27.4% (range 15.2-39.6; I^2 = 92.62%, P heterogeneity < 0.001, standard error = 0.062, p < 0.001). The rate of permanent postoperative complications was 4.1% (range 1.3-6.9; I^2 = 38.52%, P heterogeneity = 0.123, standard error = 0.014, p = 0.004). Combined use of awake craniotomy and IoMRI can help in maximizing brain tumor resection in selected patients. The technical obstacles to doing so are not severe and can be managed by experienced neurosurgery and anesthesiology teams. The benefits of bringing these technologies to bear on patients with brain tumors in or near language areas are obvious. The lack of equipoise on this topic by experienced practitioners will make it difficult to do a prospective, randomized, clinical trial. In the opinion of the authors, such a trial would be unnecessary and would deprive some patients of the benefits of the best available methods for their tumor resections

Robust thalamic nuclei segmentation method based on local diffusion magnetic resonance properties.

The thalamus is an essential relay station in the cortical-subcortical connections. It is characterized by a complex anatomical architecture composed of numerous small nuclei, which mediate the involvement of the thalamus in a wide range of neurological functions. We present a novel framework for segmenting the thalamic nuclei, which explores the orientation distribution functions (ODFs) from diffusion magnetic resonance images at 3 T. The differentiation of the complex intra-thalamic microstructure is improved by using the spherical harmonic (SH) representation of the ODFs, which provides full angular characterization of the diffusion process in each voxel. The clustering was performed using the k-means algorithm initialized in a data-driven manner. The method was tested on 35 healthy volunteers and our results show a robust, reproducible and accurate segmentation of the thalamus in seven nuclei groups. Six of them closely matched the anatomy and were labeled as anterior, ventral anterior, medio-dorsal, ventral latero-ventral, ventral latero-dorsal and pulvinar, while the seventh cluster included the centro-lateral and the latero-posterior nuclei. Results were evaluated both qualitatively, by comparing the segmented nuclei to the histological atlas of Morel, and quantitatively, by measuring the clusters' extent and the clusters' spatial distribution across subjects and hemispheres. We also showed the robustness of our approach across different sequences and scanners, as well as intra-subject reproducibility of the segmented clusters using additional two scan-rescan datasets. We also observed an overlap between the path of the main long-connection tracts passing through the thalamus and the spatial distribution of the nuclei identified with our clustering algorithm. Our approach, based on SH representations of the ODFs, outperforms the one based on angular differences between the principle diffusion directions, which is considered so far as state-of-the-art method. Our findings show an anatomically reliable segmentation of the main groups of thalamic nuclei that could be of potential use in many clinical applications

Direct cochlear nerve stimulation monitoring through evoked muscle responses during retrosigmoid vestibular schwannoma resection surgery: technical note.

Cochlear nerve preservation during surgery for vestibular schwannoma (VS) may be challenging. Brainstem auditory evoked potentials and cochlear compound nerve action potentials have clearly shown their limitations in surgeries for large VSs. In this paper, the authors report their preliminary results after direct electrical intraoperative cochlear nerve stimulation and recording of the postauricular muscle response (PAMR) during resection of large VSs. The details for the electrode setup, stimulation, and recording parameters are provided. Data of patients for whom PAMR was recorded during surgery were prospectively collected and analyzed. PAMRs were recorded in all patients at the ipsilateral vertex-earlobe scalp electrode, and in 90% of the patients they were also observed in the contralateral electrode. The optimal stimulation intensity was found to be 1 mA at 1 Hz, with a good cochlear response and an absent response from other nerves. At that intensity, the ipsilateral cochlear response had an initial peak at a mean (± SEM) latency of 11.6 ± 1.5 msec with an average amplitude of 14.4 ± 5.4 µV. One patient experienced a significant improvement in his audition, while that of the other patients remained stable. PAMR monitoring may be useful in mapping the position and trajectory of the cochlear nerve to enable hearing preservation during surgery

Comparison of MRI-based automated segmentation methods and functional neurosurgery targeting with direct visualization of the Ventro-intermediate thalamic nucleus at 7T

The ventro-intermediate nucleus (Vim), as part of the motor thalamic nuclei, is a commonly used target in functional stereotactic neurosurgery for treatment of drug-resistant tremor. As it cannot be directly visualized on routinely used magnetic resonance imaging (MRI), its clinical targeting is performed using indirect methods. Recent literature suggests that the Vim can be directly visualized on susceptibility-weighted imaging (SWI) acquired at 7T. Our work aims to assess the distinguishable Vim on 7T SWI in both healthy-population and patients and, using it as a reference, to compare it with: (1) The clinical targeting, (2) The automated parcellation of thalamic subparts based on 3T diffusion MRI (dMRI), and (3) The multi-atlas segmentation techniques. In 95.2% of the data, the manual outline was adjacent to the inferior lateral border of the dMRI-based motor-nuclei group, while in 77.8% of the involved cases, its ventral part enclosed the Guiot points. Moreover, the late MRI signature in the patients was always observed in the anterior part of the manual delineation and it overlapped with the multi-atlas outline. Overall, our study provides new insight on Vim discrimination through MRI and imply novel strategies for its automated segmentation, thereby opening new perspectives for standardizing the clinical targeting