Spontaneous unilateral spatial neglect recovery after brain tumour resection: A multimodal diffusion and rs-fMRI case report.

Patients with unilateral spatial neglect (USN) are unable to explore or to report stimuli presented in the left personal and extra-personal space. USN is usually caused by lesion of the right parietal lobe: nowadays, it is also clear the key role of structural connections (the second and the third branch of the right Superior Longitudinal Fasciculus, respectively, SLF II and III) and functional networks (Dorsal and Ventral Attention Network, respectively, DAN and VAN) in USN. In this multimodal case report, we have merged those structural and functional information derived from a patient with a right parietal lobe tumour and USN before surgery. Functional, structural and neuropsychological data were also collected 6 months after surgery, when the USN was spontaneously recovered. Diffusion metrics and Functional Connectivity (FC) of the right SLF and DAN, before and after surgery, were compared with the same data of a patient with a tumour in a similar location, but without USN, and with a control sample. Results indicate an impairment in the right SLF III and a reduction of FC of the right DAN in patients with USN before surgery compared to controls; after surgery, when USN was recovered, patient's diffusion metrics and FC showed no differences compared to the controls. This single case and its multimodal approach reinforce the crucial role of the right SLF III and DAN in the development and recovery of egocentric and allocentric extra-personal USN, highlighting the need to preserve these structural and functional areas during brain surgery.

Integrating direct electrical brain stimulation with the human connectome.

Neurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level. We used 4137 DES points derived from 612 glioma patients in combination with human connectome data-resting-state functional MRI, n = 1000 and diffusion weighted imaging, n = 284-to provide a multimodal description of the causal macroscale functional networks subtending 12 distinct behavioural domains. To probe the validity of our procedure, we (i) compared the network topographies of healthy and clinical populations; (ii) tested the predictive capacity of DES-derived networks; (iii) quantified the coupling between structural and functional connectivity; and (iv) built a multivariate model able to quantify single subject deviations from a normative population. Lastly, we probed the translational potential of DES-derived functional networks by testing their specificity and sensitivity in identifying critical neuromodulation targets and neural substrates associated with postoperative language deficits. The combination of DES and human connectome data resulted in an average 29.4-fold increase in whole brain coverage compared to DES alone. DES-derived functional networks are predictive of future stimulation points (97.8% accuracy) and strongly supported by the anatomical connectivity of subcortical stimulations. We did not observe any significant topographical differences between the patients and the healthy population at both group and single subject level. Showcasing concrete clinical applications, we found that DES-derived functional networks overlap with effective neuromodulation targets across several functional domains, show a high degree of specificity when tested with the intracranial stimulation points of a different stimulation technique and can be used effectively to characterize postoperative behavioural deficits. The integration of DES with the human connectome fundamentally advances the quality of the functional mapping provided by DES or functional imaging alone. DES-derived functional networks can reliably predict future stimulation points, have a strong correspondence with the underlying white matter and can be used for patient specific functional mapping. Possible applications range from psychiatry and neurology to neuropsychology, neurosurgery and neurorehabilitation.

The arcuate fasciculus: Combining structure and function into surgical considerations.

BACKGROUND: Two Centuries from today, Karl Friedrich Burdach attributed the nomenclature "arcuate fasciculus" to a white matter (WM) pathway connecting the frontal to the temporal cortices by arching around the Sylvian fissure. Although this label remained essentially unvaried, the concepts related to it and the characterization of the structural properties of this bundle evolved along with the methodological progress of the past years. Concurrently, the functional relevance of the arcuate fasciculus (AF) classically restricted to the linguistic domain has extended to further cognitive abilities. These features make it a relevant structure to consider in a large variety of neurosurgical procedures. OBJECTIVE: Herein, we build on our previous review uncovering the connectivity provided by the Superior Longitudinal System, including the AF, and provide a handy representation of the structural organization of the AF by considering the frequency of defined reports in the literature. By adopting the same approach, we implement an account of which functions are mediated by this WM bundle. We highlight how this information can be transferred to the neurosurgical field by presenting four surgical cases of glioma resection requiring the evaluation of the relationship between the AF and the nearby structures, and the safest approaches to adopt. CONCLUSIONS: Our cumulative overview reports the most common wiring patterns and functional implications to be expected when approaching the study of the AF, while still considering seldom descriptions as an account of interindividual variability. Given its extension and the variety of cortical territories it reaches, the AF is a pivotal structure for different cognitive functions, and thorough understanding of its structural wiring and the functions it mediates is necessary for preserving the patient's cognitive abilities during glioma resection.

Heart Team for Left Appendage Occlusion without the Use of Antithrombotic Therapy: The Epicardial Perspective.

BACKGROUND: Left atrial appendage occlusion is an increasingly proposed treatment for patients with atrial fibrillation and poor tolerance to anticoagulants. All endovascular devices require antithrombotic therapy. Anatomical and clinical variables predisposing to device-related thrombosis, as well as post-procedural peri-device leaks, could mandate the continuation or reintroduction of aggressive antithrombotic treatment. Because of the absence of foreign material inside the heart, epicardial appendage closure possibly does not necessitate antithrombotic therapy, but data of large series are missing. METHODS: Multidisciplinary team evaluation for standalone totally thoracoscopic epicardial appendage closure was done in 180 consecutive patients with atrial fibrillation and poor tolerance to antithrombotic therapy. One hundred and fifty-two patients consented (male 66.1%, mean age 76.1 ± 7.4, CHA2DS2VASc mean 5.3 ± 1.6, HASBLED mean 3.8 ± 1.1). Indications were cerebral hemorrhage (48%), gastro-intestinal bleeding (33.3%), and other bleeding (20.7%). No antithrombotic therapy was prescribed from the day of surgery to the latest follow up. RESULTS: Procedural success was 98.7%. At a mean follow up of 38.2 ± 18.8 months, cardioembolic and bleeding events were 1.3% and 0.6%, respectively. Among patients with a history of blood transfusions (41.1%), none needed further transfusions or treatment post procedure. CONCLUSION: Epicardial appendage occlusion without any antithrombotic therapy appears to be safe and effective. This strategy could be advised when minimization of bleeding risk concomitant to stroke prevention is needed.

Segregated circuits for phonemic and semantic fluency: A novel patient-tailored disconnection study.

Phonemic and semantic fluency are neuropsychological tests widely used to assess patients' language and executive abilities and are highly sensitive tests in detecting language deficits in glioma patients. However, the networks that are involved in these tasks could be distinct and suggesting either a frontal (phonemic) or temporal (semantic) involvement. 42 right-handed patients (26 male, mean age = 52.5 years, SD=±13.3) were included in this retrospective study. Patients underwent awake (54.8%) or asleep (45.2%) surgery for low-grade (16.7%) or high-grade-glioma (83.3%) in the frontal (64.3%) or temporal lobe (35.7%) of the left (50%) or right (50%) hemisphere. Pre-operative tractography was reconstructed for each patient, with segmentation of the inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), third branch of the superior longitudinal fasciculus (SLF-III), frontal aslant tract (FAT), and cortico-spinal tract (CST). Post-operative percentage of damage and disconnection of each tract, based on the patients' surgical cavities, were correlated with verbal fluencies scores at one week and one month after surgery. Analyses of differences between fluency scores at these timepoints (before surgery, one week and one month after surgery) were performed; lesion-symptom mapping was used to identify the correlation between cortical areas and post-operative scores. Immediately after surgery, a transient impairment of verbal fluency was observed, that improved within a month. Left hemisphere lesions were related to a worse verbal fluency performance, being a damage to the left superior frontal or temporal gyri associated with phonemic or semantic fluency deficit, respectively. At a subcortical level, disconnection analyses revealed that fluency scores were associated to the involvement of the left FAT and the left frontal part of the IFOF for phonemic fluency, and the association was still present one month after surgery. For semantic fluency, the correlation between post-surgery performance emerged for the left AF, UF, ILF and the temporal part of the IFOF, but disappeared at the follow-up. This approach based on the patients' pre-operative tractography, allowed to trace for the first time a dissociation between white matter pathways integrity and verbal fluency after surgery for glioma resection. Our results confirm the involvement of a frontal anterior pathway for phonemic fluency and a ventral temporal pathway for semantic fluency. Finally, our longitudinal results suggest that the frontal executive pathway requires a longer interval to recover compared to the semantic one.

The role of the default mode network in longitudinal functional brain reorganization of brain gliomas.

The study of patients after glioma resection offers a unique opportunity to investigate brain reorganization. It is currently unknown how the whole-brain connectomic profile evolves longitudinally after surgical resection of a glioma and how this may be associated with tumor characteristics and cognitive outcome. In this longitudinal study, we investigate the impact of tumor lateralization and grade on functional connectivity (FC) in highly connected networks, or hubs, and cognitive performance. Twenty-eight patients (17 high-grade, 11 low-grade gliomas) underwent longitudinal pre/post-surgery resting-state fMRI scans and neuropsychological assessments (73 total measures). FC matrices were constructed considering as functional hubs the default mode (DMN) and fronto-parietal networks. No-hubs included primary sensory functional networks and any other no-hubs nodes. Both tumor hemisphere and grade affected brain reorganization post-resection. In right-hemisphere tumor patients, regardless of grade and relative to left-hemisphere gliomas, FC increased longitudinally after the intervention, both in terms of FC within hubs (phubs = 0.0004) and FC between hubs and no-hubs (phubs-no-hubs = 0.005). Regardless of tumor side, only lower-grade gliomas showed longitudinal FC increases relative to high-grade tumors within a precise hub network, the DMN. The neurocognitive profile was longitudinally associated with spatial features of the connectome, mainly within the DMN. We provide evidence that clinical glioma features, such as lateralization and grade, affect post-surgical longitudinal functional reorganization and cognitive recovery. The data suggest a possible role of the DMN in supporting cognition, providing useful information for prognostic prediction and surgical planning.

Classifyber, a robust streamline-based linear classifier for white matter bundle segmentation.

Virtual delineation of white matter bundles in the human brain is of paramount importance for multiple applications, such as pre-surgical planning and connectomics. A substantial body of literature is related to methods that automatically segment bundles from diffusion Magnetic Resonance Imaging (dMRI) data indirectly, by exploiting either the idea of connectivity between regions or the geometry of fiber paths obtained with tractography techniques, or, directly, through the information in volumetric data. Despite the remarkable improvement in automatic segmentation methods over the years, their segmentation quality is not yet satisfactory, especially when dealing with datasets with very diverse characteristics, such as different tracking methods, bundle sizes or data quality. In this work, we propose a novel, supervised streamline-based segmentation method, called Classifyber, which combines information from atlases, connectivity patterns, and the geometry of fiber paths into a simple linear model. With a wide range of experiments on multiple datasets that span from research to clinical domains, we show that Classifyber substantially improves the quality of segmentation as compared to other state-of-the-art methods and, more importantly, that it is robust across very diverse settings. We provide an implementation of the proposed method as open source code, as well as web service.

Trans-thoracic versus retropleural approach for symptomatic thoracic disc herniations: comparative analysis of 94 consecutive cases.

PURPOSE: The authors illustrate their results in the surgical treatment of symptomatic thoracic disc herniations (TDHs) by comparing the traditional open to the less invasive retropleural lateral approaches. METHODS: Retrospective review of 94 consecutive cases treated at a single Institution between 1988 and 2014. Fifty-two patients were males, 42 females, mean age was 53.9 years. Mean follow-up was 46.9 months (12-79 months). 33 patients were diagnosed with a giant thoracic disc herniation (GTDH). Upon admission, the most common symptoms were: motor impairment (91.4%, n = 86), neuropathic radicular pain with VAS > 4 (50%), bladder and bowel dysfunction (57.4% and 41.4% respectively) and sensory disturbances (29.7%). The surgical approach was based upon level, laterality and presence or absence of calcified lesions. RESULTS: Decompression was performed in 7 cases via a thoraco-laparo-phrenotomy and in 87 cases via an antero-lateral thoracotomy. Out of the latter cases, 49 (56%) were trans-thoracic trans-pleural approaches (TTA) and 38 (44%) were less invasive retropleural approaches (MIRA). At follow-up, there were 59.5% neurologically intact patients according to the McCormick Scale, while 64.8% and 67% had no bladder or bowel dysfunction respectively. Complications occurred in 24 patients (25.5%). Pulmonary complications were the commonest (12.7%) with pleural effusion being significantly more common in patients treated with TTA compared to MIRA (20% vs 5.2%: X2 4.13 P:0.042). Severe post-operative neuralgia (VAS 7-10) was also significantly more frequent in the TTA group (22.4% vs 2.6% X2 7.07 p 0.0078). CONCLUSIONS: MIRA is a safe and effective technique to obtain adequate TDH decompression and is associated with lower morbidity compared to TTA.

Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.

BACKGROUND: Functional preoperative planning for resection of intrinsic brain tumors in eloquent areas is still a challenge. Predicting subcortical functional framework is especially difficult. Direct electrical stimulation (DES) is the recommended technique for resection of these lesions. A reliable probabilistic atlas of the critical cortical epicenters and subcortical framework based on DES data was recently published. OBJECTIVE: To propose a pipeline for the automated alignment of the corticosubcortical maps of this atlas with T1-weighted MRI. METHODS: To test the alignment, we selected 10 patients who underwent resection of brain lesions by using DES. We aligned different cortical and subcortical functional maps to preoperative volumetric T1 MRIs (with/without gadolinium). For each patient we quantified the quality of the alignment, and we calculated the match between the location of the functional sites found at DES and the functional maps of the atlas. RESULTS: We found an accurate brain extraction and alignment of the functional maps with both the T1 MRIs of each patient. The matching analysis between functional maps and functional responses collected during surgeries was 88% at cortical and, importantly, 100% at subcortical level, providing a further proof of the correct alignment. CONCLUSION: We demonstrated quantitatively and qualitatively the reliability of this tool that may be used for presurgical planning, providing further functional information at the cortical level and a unique probabilistic prevision of distribution of the critical subcortical structures. Finally, this tool offers the chance for multimodal planning through integrating this functional information with other neuroradiological and neurophysiological techniques.

The quality of measurement properties of neurocognitive assessment in brain tumor clinical trials over the last 30 years: a COSMIN checklist-based approach.

PURPOSE: To provide an exhaustive review of the neuropsychological examination as conducted in brain tumor clinical trials over the last 30 years and to provide objective ratings about the reliability and suitability of such tests in neurooncological research and clinical practice. METHODS: Methodologies and tools provided by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) were exploited in order to assess the measurement properties of questionnaires and performance-based instruments used to evaluate cognitive functioning in brain tumor clinical trials from 1997 to 2017. RESULTS: Twenty-six brain tumor clinical trials were analyzed and an overall set of 10 neuropsychological tests was identified. A list of 24 studies concerning the reliability of such tests was analyzed. Reliability and level of evidence scores for each study and for each test were obtained. The results revealed relevant faults about the quality of measurements and the suitability of the neurocognitive assessment batteries most commonly used in brain tumor clinical trials. CONCLUSION: Our findings suggest that the cognitive assessment in brain tumor clinical trials should be implemented according to specific endpoints and should be addressed to investigate all the cognitive domains known to be affected by brain tumor and treatment.

Effects of supra-total resection in neurocognitive and oncological outcome of high-grade gliomas comparing asleep and awake surgery.

PURPOSE: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection (EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery. METHODS: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent to an extensive neuropsychological assessment before surgery (time_1), 1-week (time_2) and 4-months (time_3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overall survival (OS) between the two groups was conducted. RESULTS: Statistical analyses showed no differences between groups at time_2 and time_3 in each cognitive domain, excluding selective attention that resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time_3, similar for both groups. Assessment of time_3 in respect to time_1 never showed differences (all ps > .074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p < .05), with an influence on OS (p < .05). Indeed, patients of AWg showed a significant longer OS in comparison to those in the ASg (p < .01). This result was confirmed even considering only wildtype Glioblastoma (p < .05). CONCLUSION: These results indicate that awake surgery, and in general a supra-total resection of enhancing area, can improve OS in HGGs patients, preserving neuro-cognitive profile and quality of life.

Whole-Brain Network Connectivity Underlying the Human Speech Articulation as Emerged Integrating Direct Electric Stimulation, Resting State fMRI and Tractography.

Production of fluent speech in humans is based on a precise and coordinated articulation of sounds. A speech articulation network (SAN) has been observed in multiple brain studies typically using either neuroimaging or direct electrical stimulation (DES), thus giving limited knowledge about the whole brain structural and functional organization of this network. In this study, seven right-handed patients underwent awake surgery resection of low-grade gliomas (4) and cavernous angiomas. We combined pre-surgical resting state fMRI (rs-fMRI) and diffusion MRI together with speech arrest sites obtained intra-operatively with DES to address the following goals: (i) determine the cortical areas contributing to the intrinsic functional SAN using the speech arrest sites as functional seeds for rs-fMRI; (ii) evaluate the relative contribution of gray matter terminations from the two major language dorsal stream bundles, the superior longitudinal fasciculus (SLF III) and the arcuate fasciculus (AF); and (iii) evaluate the possible pre-surgical prediction of SAN with rs-fMRI. In all these right-handed patients the intrinsic functional SAN included frontal, inferior parietal, temporal, and insular regions symmetrically and bilaterally distributed across the two hemispheres regardless of the side (four right) of speech arrest evocation. The SLF III provided a much higher density of terminations in the cortical regions of SAN in respect to AF. Pre-surgical rs-fMRI data demonstrated moderate ability to predict the SAN. The set of functional and structural data provided in this multimodal study characterized, at a whole-brain level, a distributed and bi-hemispherical network subserving speech articulation.