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

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

Sympathetic activity and early mobilization in patients in intensive and intermediate care with severe brain injuries: a preliminary prospective randomized study.

Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. Blood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. The study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432 . Date of registration: 08.03.2016. Retrospectively registered

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

Towards improving the safety and diagnostic yield of stereotactic biopsy in a single centre

Background: Previously, we reported on our single centre results regarding the diagnostic yield of stereotactic needle biopsies of brain lesions. The yield then (1996-2006) was 89.4%. In the present study, we review and evaluate our experience with intraoperative frozen-section histopathologic diagnosis on-demand in order to improve the diagnostic yield. Methods:

Mapping the Interactions between a RUN Domain from DENND5/Rab6IP1 and Sorting Nexin 1

Eukaryotic cells have developed a diverse repertoire of Rab GTPases to regulate vesicle trafficking pathways. Together with their effector proteins, Rabs mediate various aspects of vesicle formation, tethering, docking and fusion, but details of the biological roles elicited by effectors are largely unknown. Human Rab6 is involved in the trafficking of vesicles at the level of Golgi via interactions with numerous effector proteins. We have previously determined the crystal structure of Rab6 in complex with DENND5, alternatively called Rab6IP1, which comprises two RUN domains (RUN1 and RUN2) separated by a PLAT domain. The structure of Rab6/RUN1-PLAT (Rab6/R1P) revealed the molecular basis for Golgi recruitment of DENND5 via the RUN1 domain, but the functional role of the RUN2 domain has not been well characterized. Here we show that a soluble DENND5 construct encompassing the RUN2 domain binds to the N-terminal region of sorting nexin 1 by surface plasmon resonance analyses

Mouse Transgenesis Identifies Conserved Functional Enhancers and cis-Regulatory Motif in the Vertebrate LIM Homeobox Gene Lhx2 Locus

The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs) in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG), recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs) associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers